Hydrochloric Acid → Florfenicol amine

HRID 507889노트

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HRID 507889 반응식
C([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([S:18]([CH3:21])(=[O:20])=[O:19])=[CH:14][CH:13]=2)[O:7]C1(C)C)(=O)CC.Cl.[OH-].[Na+]>C(Cl)Cl.O>[CH3:21][S:18]([C:15]1[CH:14]=[CH:13][C:12]([C@@H:8]([OH:7])[C@H:9]([NH2:5])[CH2:10][F:11])=[CH:17][CH:16]=1)(=[O:20])=[O:19]

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68470798(4S,5R)-3-propionyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine2회

생성물 1

HCID 156406Florfenicol amine

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매2회

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온도
95 °C

실험 절차

Methylene chloride (450 mL) distills from a solution of (4S,5R)-3-propionyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine (Compound IX: R1 is methylsulfonyl, R2 and R3 are methyl and R4 is ethyl) (50.0 g, 0.1456 moles) after addition of water (300 mL) containing 20% hydrochloric acid and heating to 90-100° C. for 2-4 hours. Adjusting the pH to greater than 12 by addition of sodium hydroxide and extraction with methylene chloride (350 mL) yields a solution of (1R,2S)-1-[4-(methylsulfonyl)phenyl]-2-amino-3-fluoro-1-propanol (Compound Xa). Methanol (150 mL) replaces methylene chloride which distills off. Addition of methyl dichloroacetate (52.0 g, 0.3640 moles) and triethylamine (11.0 g, 0.1092 moles) with agitation for 12-16 hours at 20-25° C. then addition of water (150 mL) and toluene (100 mL) precipitates the crude product. Filtration, washing with water (75 mL) and toluene (125 mL) then dissolution in water (50 mL) and isopropanol (100 mL) at reflux, cooling to 20-25° C., filtration of the solids, washing with 1 to 1 water/isopropanol (50 mL) then drying gives pure (1R,2S)-2-dichloroacetamido-3-fluoro-1-[4-(methylsulfonyl)phenyl]-1-propanol (Florfenicol).

출처 및 근거

ORD 기록
ord-0bd849af16e84068a221814228ee7f16
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786329B2

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