Hydrochloric Acid → HCID 54240884, compound

HRID 964518Notes

Reaction equation

HRID 964518 reaction equation
C([O:4][CH:5]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])[C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14](=[O:16])[CH3:15])(=O)C.P([O-])(O)(O)=O.[K+].P([O-])([O-])(O)=O.[K+].[K+].Cl>C1(C)C=CC=CC=1>[C:14]([NH:13][C:7]1[CH:8]=[CH:9][C:10]([Cl:12])=[CH:11][C:6]=1[C@H:5]([OH:4])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[Cl:23])(=[O:16])[CH3:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24450Potassium Phosphate, DibasicHCID 516951Monobasic potassium phosphateHCID 54108557HCID 54108557, compound

Product 1

HCID 54240884HCID 54240884, compoundYield 22.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture of 2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl acetate (2.0 g), toluene (30 ml), 0.1M potassium dihydrogen phosphate (aq. sol., 20 ml) and 0.1M potassium monohydrogen phosphate (aq. sol., 20 ml) was added Lipase AP6 (Amano Pharmaceutical) (0.8 g) and the whole mixture was stirred vigorously at room temperature for 6 days. To this reaction mixture was added 1N-hydrochloric acid (50 ml) to stop the reaction, followed by extraction with ethyl-acetate (50 ml). The ethyl acetate layer was washed with aqueous sodium hydrogen carbonate solution and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:methylene chloride:ethyl acetate=4:1:1-1:1:1). The unreacted 2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl acetate (1.28 g) was recovered from the first fraction. Then, (S)-2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl alcohol (0.40 g) was obtained as oil from the second fraction. The optical purity of this product as determined by high performance liquid column chromatography using a chiral column [ULTRON ES-OVM (Shinwa Chemical Industries, Ltd.)] was 85% ee. This (S)-2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl alcohol of 86 (85)% ee was dissolved in hexane-diethyl ether and the crystals (47 mg) that had separated out were separated. The mother liquor was distilled under reduced pressure to provide (S)-2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl alcohol of higher purity as oil (0.31 g). Optical purity 96.4% ee.

Workup

  1. additionwas added Lipase AP6 (Amano Pharmaceutical) (0.8 g)
  2. customthe reaction
  3. extractionfollowed by extraction with ethyl-acetate (50 ml)
  4. washThe ethyl acetate layer was washed with aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled off under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (hexane:methylene chloride:ethyl acetate=4:1:1-1:1:1)
  8. customThe unreacted 2-acetylamino-5-chloro-α-(2-chlorophenyl)benzyl acetate (1.28 g) was recovered from the first fraction

Sources & evidence

ORD record
ord-29f88c0a237f444cb8d52ce7f0b18d2b
Source dataset
uspto-grants-1998_06
Patent number
US05770438

Reaction notes

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