(4S)-4-methyloxolan-2-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To EtOH (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in EtOH (20 ml). The ice bath was removed and the reaction allowed to reach RT. After 2 h of stirring the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in EtOH (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach RT was concentrated the residue redissolved in CH2Cl2 washed with sat. aq. NaHCO3 solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to that described in Example 72g), the title compound is obtained starting from 3.2 g of 2(S)-tert-butoxycarbonylamino-4(R)-methyl-6-triisopropylsilyloxyhexanal (Rf (D)=0.36), which is prepared by processes analogous to those described in Examples 72h to 72n), starting from (S)-3-methylbutyrolactone, and is purified by FC over 400 g of silica gel (mobile phase gradient from E to B), the two stereoisomers being separated. This gives the title compound (diastereomer I): Rf (A)=0.58; and diastereomer II: Rf (A)=0.47. is obtained is prepared by processes analogous to is purified by FC over 400 g of silica gel (mobile phase gradient from E to B) the two stereoisomers being separated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to that described in Example 72g), the title compound is obtained starting from 3.2 g of 2(S)-tert-butoxycarbonylamino-4(R)-methyl-6-triisopropylsilyloxyhexanal (Rf (D)=0.36), which is prepared by processes analogous to those described in Examples 72h to 72n), starting from (S)-3-methylbutyrolactone, and is purified by FC over 400 g of silica gel (mobile phase gradient from E to B), the two stereoisomers being separated. This gives the title compound (diastereomer I): Rf (A)=0.58; and diastereomer II: Rf (A)=0.47. is obtained is prepared by processes analogous to is purified by FC over 400 g of silica gel (mobile phase gradient from E to B) the two stereoisomers being separated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quantitative). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with sat. aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with saturated aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with saturated aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quantitative). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with sat. aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To EtOH (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in EtOH (20 ml). The ice bath was removed and the reaction allowed to reach RT. After 2 h of stirring the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in EtOH (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach RT was concentrated the residue redissolved in CH2Cl2 washed with sat. aq. NaHCO3 solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a manner analogous to that described in Example 72g), the title compound is obtained starting from 3.2 g of 2(S)-tert-butoxycarbonylamino-4(R)-methyl-6-triisopropylsilyloxyhexanal (Rf (D)=0.36), which is prepared by processes analogous to those described in Examples 72h to 72n), starting from (S)-3-methylbutyrolactone, and is purified by FC over 400 g of silica gel (mobile phase gradient from E to B), the two stereoisomers being separated. This gives the title compound (diastereomer I): Rf (A)=0.58; and diastereomer II: Rf (A)=0.47. is obtained is prepared by processes analogous to is purified by FC over 400 g of silica gel (mobile phase gradient from E to B) the two stereoisomers being separated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quantitative). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with sat. aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with sat. aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To ethanol (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in ethanol (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+. The ice bath was removed to reach room temperature was concentrated the residue redissolved in dichloromethane washed with saturated aq. sodium hydrogencarbonate solution dried (Na2SO4) concentrated