Acetic Anhydride → HCID 57309346, compound

HRID 728892Notes

Reaction equation

HRID 728892 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 25 minutes to a solution of 20.2 g of 2, 16.83 ml of triethylamine and 0.62 g of 4-(dimethylamino)-pyridine in 300 ml of dichloromethane. After 30 minutes,the mixture is washed twice with ice-cold 2N 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 hotin 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 roomtemperature for 30 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 2N 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 hotin hexane/ ethyl acetate 4:1
  6. temperatureOn cooling slowly
  7. customto 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°
  8. waitkept at that temperature for one hour
  9. filtrationFiltration

Sources & evidence

ORD record
ord-9af890314726444ba74262bf18424b48
Source dataset
uspto-grants-1991_09
Patent number
US05051413

Reaction notes

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