ethyl 2-phenylmethoxyacetate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Diethyl oxalate (5.66 g, 38.7 mmol) and ethyl benzyloxyacetate (7.52 g, 38.7 mmol) in dry tetrahydrofuran (60 ml) were treated at 22° C. with sodium hydride (1.70 g of a 60% dispersion in mineral oil, 42.5 mmol) and the condensation product was reacted with a mixture of intermediate 11, 2-(2-(methylthio)ethoxy)propanamidine hydrochloride salt, (7.70 g, 38.7 mmol) in a solution of sodium ethoxide (19.3 mmol, prepared from 0.445 g of sodium) in ethanol (50 ml) to give 2.29 g (15% yield) of the title ester as a clear oil after chromatography on silica gel. 1HNMR 400 MHz (CDCl3) δ ppm: 1.33 (3H, t, J=7.1 Hz, CH3), 1.54 (3H, d, J=7.1 Hz, CH3), 2.16 (3H, s, SCH3), 2.7–2.8 (2H, m, CH2), 3.54 (1H, m, CH), 3.86 (1H, m, CH), 4.37 (2H, q, J=7.1 Hz, OCH2), 4.47 (1H, q, J=7.1 Hz, OCH), 5.34 (2H, ABq, JAB=11.0 Hz, OCH2), 7.37 (3H, m, aromatics), 7.49 (2H, m, aromatics). MS (ESI+) m/z 393 [M+H+].

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Diethyl oxalate (7.66 g, 52.4 mmol) and ethyl benzyloxyacetate (10.2 g, 52.5 mmol) in dry tetrahydrofuran (70 ml) were treated at 22° C. with sodium hydride (2.31 g of a 60% dispersion in mineral oil, 57.7 mmol) and ethanol (40 μl). The tetrahydrofuran was then evaporated under reduced pressure and the residue treated with a mixture of 2-iminopiperidine hydrochloride (7.05 g, 52.2 mmol) in a solution of sodium ethoxide (26.0 mmol, prepared from 0.60 g of sodium) in ethanol (70 ml) and the resulting mixture heated at 60° C. for 4 h. Acetic acid (2 ml) was added and the ethanol was evaporated under reduced pressure. The residue was diluted with ethyl acetate washed successively with saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Chromatography on silica gel (elution toluene/ethyl acetate 1:1) gave 2.37 g (14% yield) of the title ester as white crystals; mp 97–99° C. (ethyl acetate-hexane). 1HNMR 400 MHz (CDCl3) δ (ppm): 1.33 (3H, t, J=7.1 Hz, CH3), 1.92 (2H, m, CH2), 2.0 (2H, m, CH2), 2.97 (2H, t, J=6.8 Hz, CH2), 4.02 (2H, t, J=6.3 Hz, NCH2), 4.36 (2H, q, J=7.1 Hz, OCH2), 5.27 (2H, s, OCH2), 7.3–7.51 (5H, m, aromatics). Anal. Calcd for C18H20N2O4: C, 65.84; H, 6.14; N, 8.53. Found: C 65.72, H 6.33, N 8.41. The tetrahydrofuran was then evaporated under reduced pressure the ethanol was evaporated under reduced pressure The residue was diluted with ethyl acetate washed successively with saturated sodium bicarbonate and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure

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

Procedure: The 4-alkoxy-2-morpholino-5-pyrimidinols (D represents alkoxy) can be prepared by reacting a 1:1 mixture of ethyl benzyloxyacetate and ethyl formate with sodium hydride in toluene and the product is then reacted with 4-morpholinecarboximidamide sulfate to give 5-benzyloxy-2-morpholino-4-pyrimidinol. The latter compound is converted to 5-benzyloxy-4-chloro-2-morpholinopyrimidine by reaction with phosphorus oxychloride. The ring chlorine is then replaced by an alkoxy group with an alkali alkoxide to give 4-alkoxy-5-benzyloxy-2-morpholinopyrimidine. The benzyloxy group is then converted to the OH group by hydrogenation in the presence of a solvent and a hydrogenation catalyst.

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: This compound was prepared in a manner analogous to the compound of Example 16 from 2,4-dichlorophenylacetonitrile and ethyl benzyloxyacetate, 3.77 gms, mp. 171°-172° C.

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

Procedure: This compound was prepared in a manner analogous to the compound of Example 16 from 2,4-dichlorophenylacetonitrile and ethyl benzyloxyacetate, 3.77 gms, mp. 171°-172° C.

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

Procedure: This compound was prepared in a manner analogous to the compound of Example 16 from 2,4-dichlorophenylacetonitrile and ethyl benzyloxyacetate, 3.77 gms, mp. 171°-172° C.

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a flame-dried flask were placed dry THF (4 ml) and diisopropylamine (1.21 g, 0.012 mol). n-Butyllithium (1.55M in hexane, 7.7 ml, 0.012 mol) was added dropwise at -10° C. under argon. After stirring for 0.5 h at 0° C., a solution of ethylphenylmethoxyacetate (2.33 g, 0.012 mol) in dry THF (4 ml) was added dropwise at -78° C. After one h methyl 5-chloro-2-phenylmethoxybenzoate (2.21 g, 0.008 mol) in dry THF (4 ml) was added. Stirring was continued for an additional 2 h at -78° C. and the reaction mixture was quenched with 2 ml of EtOH at -20° C. The quenched mixture was poured into 50 ml of 10% aqueous HCl solution and extracted with ether. The ether layer was washed with water, dried (Na2SO4), filtered and concentrated under reduced pressure affording a light yellow oil. Purification by flash chromatography (silica gel) using toluene-CHCl3 (5:1) as eluent afforded 1.96 g (56%) of ethyl 5-chloro-β-oxo-α,2-bis(phenylmethoxy)benzenepropanoate as white crystals (EtOH): mp 64°-65° C.; IR (KBr) 1735 (ester) and 1685 (conjugated carbonyl) cm-1 ; NMR (CDCl3, 90 MHz) δ 1.16 (t, 3H, OCH2CH3) 4.13 (q, 2H, OCH2CH3), 4.55 (dd, 1H, OCH2Ph, JAB =12.6 Hz), 4.60 (dd, 1H, OCH2Ph, JAB =12.6 Hz), 5.07 (s, 2H, OCH2Ph), 5.28 (s, 1H, CHCO2Et), 6.85 (d, 1H, ArH, J=8.9 Hz), 7.05-7.50 (m, 11H, ArH), 7.64 (d, 1H, ArH, J=2.5 Hz). Anal calcd. for C25H23ClO5 : C, 68.41; H, 5.28; Cl, 8.07. Found: C, 68.14; H, 5.28; Cl, 8.09. In a flame-dried flask were placed dry Stirring was continued for an additional 2 h at -78° C. the reaction mixture was quenched with 2 ml of EtOH at -20° C The quenched mixture was poured into 50 ml of 10% aqueous HCl solution extracted with ether The ether layer was washed with water dried (Na2SO4) filtered concentrated under reduced pressure affording a light yellow oil Purification by flash chromatography (silica gel)