Hydrochloric Acid → Florfenicol amine

HRID 507889ノート

反応式

HRID 507889 の反応式
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]

参加物

6

反応物 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68470798(4S,5R)-3-propionyl-2,2-dimethyl-4-fluoromethyl-5-[4-(methylsulfonyl)phenyl]-1,3-oxazolidine2 回

生成物 1

HCID 156406Florfenicol amine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
95 °C

実験手順

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).

出典と根拠

ORDレコード
ord-0bd849af16e84068a221814228ee7f16
出典データセット
uspto-grants-2010_08
特許番号
US07786329B2

反応ノート

読み込み中…