Acetic Anhydride → HCID 57309346, compound

HRID 1682323Notes

Reaction equation

HRID 1682323 reaction equation
C(OC(=O)C)(=O)C.[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH:20]=[CH:21][CH2:22][CH2:23][C:24](OCC)=[O:25])[CH2:18][O:17][C:16]1([CH3:30])[CH3:29])=[O:14])([CH3:11])([CH3:10])[CH3:9].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH:20]=[CH:21][CH2:22][CH2:23][CH2:24][OH:25])[CH2:18][O:17][C:16]1([CH3:30])[CH3:29])=[O:14])([CH3:11])([CH3:10])[CH3:9]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 57155621HCID 57155621, compound

Product 1

HCID 57309346HCID 57309346, compoundYield 85.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-12 °C

Procedure

A solution of 11.42 ml of acetic anhydride in 50 ml of dichloromethane is added dropwise at 0°-3° within a period of minutes to a solution of 20.2 g of 2, 16.83 ml of triethylamine and 0.62 g of 4-(dimethylamino)-pyridine in 0 ml of dichloromethane. After 30 minutes, the mixture is washed twice with ice-cold 2 N hydrochloric acid and twice with 10% sodium chloride solution. The aqueous phases are extracted with 100 ml of dichloromethane. The organic phases are dried over sodium sulphate and concentrated by evaporation, and the residue is dissolved hot in hexane/ethyl acetate 4:1. On cooling slowly to approximately 30° there crystallise 1.82 g of racemic (2R*,2S*)-2-formamino-3-acetoxy-4-methyl-4-pentenoic acid ethyl ester having a melting point of 98°-106°. The mother liquor is slowly cooled to -12° C. and kept at that temperature for one hour. Filtration yields 15.04 g of acetate 3, m.p. 73°-75°, [α]D =-75.6° (c=1, CHCl3), analysis by gas chromatography (Chirasil®-L-Val, 160°-180°, 1° per minute): (2R,3S)-isomer 93.5% (Tret =14.5 minutes), (2S,3R)-isomer 2.2% (Tret =14.8 minutes), (2R,3R)-isomer 2.2% (Tret =16.8 minutes), (2S,3S)-isomer 2.1% (Tret =17.1 minutes). 20.64 g of anhydrous potassium carbonate are added at -16° to a solution of (2R,3S)-2-formylamino-3-acetoxy-4-methyl-4-pentenoic acid ethyl ester (3) in 400 ml of absolute ethanol. After stirring at -18° to -11° C. for 4 hours, 500 ml of buffer solution (1 molar, phosphate, pH=7) are added dropwise. The mixture is stirred at room temperature for 0 minutes and extracted three times with 350 ml of dichloromethane each time. The organic phases are dried over sodium sulphate and concentrated by evaporation, and the residue is chromatographed on 1 kg of silica gel using hexane/ethyl acetate 1:2 as eluant, yielding 9.8 g of alcohol 1.

Workup

  1. washthe mixture is washed twice with ice-cold 2 N hydrochloric acid and twice with 10% sodium chloride solution
  2. extractionThe aqueous phases are extracted with 100 ml of dichloromethane
  3. dry with materialThe organic phases are dried over sodium sulphate
  4. concentrationconcentrated by evaporation
  5. dissolutionthe residue is dissolved hot in hexane/ethyl acetate 4:1
  6. temperatureOn cooling slowly to approximately 30° there crystallise 1.82 g of racemic (2R*,2S*)-2-formamino-3-acetoxy-4-methyl-4-pentenoic acid ethyl ester having a melting point of 98°-106°
  7. waitkept at that temperature for one hour
  8. filtrationFiltration

Sources & evidence

ORD record
ord-d9accf557d8a4ec39592049b02010d6b
Source dataset
uspto-grants-1992_12
Patent number
US05175344

Reaction notes

Loading…