amino benzoate

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

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

Procedure: Phenylacetylene is subject to 1) hydroxymethylation followed by 2) Lindlar reduction to yield cis-cinnamyl alcohol. ##STR6## 3) The cis-cinnamyl alcohol is subjected to the titanium-catalyzed epoxidation process to yield (2S,3R)-epoxy alcohol. ##STR7## 4) This epoxy alcohol is oxidized with RuCl3 and NaIO4, and 5) the reaction product converted to the methyl ester of the epoxide with ethereal diazomethane. 6) This methyl ester of the epoxide is transformed into the desired hydroxyazide by epoxide cleavage using azidotrimethylsilane and a catalytic amount of zinc chloride followed by acid hydrolysis. ##STR8## 7) The hydroxy azide is transformed into azido benzoate and hydrogenated in methanol to produce amino benzoate. 8) The amino benzoate is rearranged to give the product. ##STR9## Modifications in this method have also been described by Denis, J. N. et al., "An Improved Synthesis of the Taxol Side Chain and of RP56976", J. Org. Chem 55, 1957-1959 (1990).

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

Procedure: Phenylacetylene is subject to 1) hydroxymethylation followed by 2) Lindlar reduction to yield cis-cinnamyl alcohol. ##STR6## 3) The cis-cinnamyl alcohol is subjected to the titanium-catalyzed epoxidation process to yield (2S,3R)-epoxy alcohol. ##STR7## 4) This epoxy alcohol is oxidized with RuCl3 and NaIO4, and 5) the reaction product converted to the methyl ester of the epoxide with ethereal diazomethane. 6) This methyl ester of the epoxide is transformed into the desired hydroxyazide by epoxide cleavage using azidotrimethylsilane and a catalytic amount of zinc chloride followed by acid hydrolysis. ##STR8## 7) The hydroxy azide is transformed into azido benzoate and hydrogenated in methanol to produce amino benzoate. 8) The amino benzoate is rearranged to give the product. ##STR9## Modifications in this method have also been described by Denis, J. N. et al., "An Improved Synthesis of the Taxol Side Chain and of RP56976", J. Org. Chem 55, 1957-1959 (1990).

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

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

Procedure: To a solution of O-Benzoylhydroxylamine hydrochloride (85 mg, 0.49 mmol, prepared as described in the procedure of Carpino et al., 1959) in water (5 ml) was added at room temperature a 1 M solution of sodium bicarbonate until the effervescence ended. The organic material was extracted three times with CH2Cl2 (10 ml per extraction). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure to give O-Benzoylhydroxylamine (49 mg, 73%). In a second flask Z-Ala-Ala-Asn-OH (19) (130 mg, 0.318 mmol) was dissolved in a mixture of dry THF (5 ml) and dry DMF (3 ml). To this stirred solution were added isobutyl chloroformate (41 μl, 0.318 mmol) and NMM (35 μl, 0.318 mmol) at −15° C. After stirring for 15 minutes O-Benzoylhydroxylamine in dry THF (2 ml) was added and the mixture was stirred 14 h, during which time it was allowed to warm to room temperature. The solvent was evaporated in vacuo and the obtained residue was washed with cold KHSO4 (5% in water, 5 ml). The precipitate was dissolved in ethyl acetate (10 ml), washed with water (3×5 ml) and dried over Na2SO4. After filtration the solvent was evaporated under reduced pressure. The crude compound was purified by preparative HPLC to give the product as an oil (77 mg, 46%).—TLC (MeOH/CHCl3, 1:9): Rf=0.31.—1H NMR (500 MHz, DMSO-d6): δ=1.19 (d, 3 H, J=6.9 Hz, CH3), 1.21 (d, 3 H, J=7.0 Hz, CH3), 2.78-2.96 (m, 2 H, CHCH2), 4.04-4.08 (m, 1 H, CH), 4.25-4.34 (m, 1 H, CH), 4.48-4.55 (m, 1 H, CH), 4.97-5.04 (m, 2 H, CH2O), 7.26-7.42 (m, 10 H, aryl-H), 7.93 (d, 2 H, J=8.2 Hz, NH).—MS (EI) m/z (%): 528 [M+H+], 550 [M+Na+], 566 [M+K+]. The organic material was extracted three times with CH2Cl2 (10 ml per extraction) The combined organic layers were dried over Na2SO4 concentrated under reduced pressure

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

Procedure: Phenylacetylene is subject to 1) hydroxymethylation followed by 2) Lindlar reduction to yield cis-cinnamyl alcohol. ##STR6## 3) The cis-cinnamyl alcohol is subjected to the titanium-catalyzed epoxidation process to yield (2S,3R)-epoxy alcohol. ##STR7## 4) This epoxy alcohol is oxidized with RuCl3 and NaIO4, and 5) the reaction product converted to the methyl ester of the epoxide with ethereal diazomethane. 6) This methyl ester of the epoxide is transformed into the desired hydroxyazide by epoxide cleavage using azidotrimethylsilane and a catalytic amount of zinc chloride followed by acid hydrolysis. ##STR8## 7) The hydroxy azide is transformed into azido benzoate and hydrogenated in methanol to produce amino benzoate. 8) The amino benzoate is rearranged to give the product. ##STR9## Modifications in this method have also been described by Denis, J. N. et al., "An Improved Synthesis of the Taxol Side Chain and of RP56976", J. Org. Chem 55, 1957-1959 (1990).