Methanol → HCID 58280450, 화합물

HRID 1879476노트

반응식

HRID 1879476 반응식
C([O:3][C:4]([CH:6]1[CH2:10][CH2:9][S:8](=[O:12])(=[O:11])[N:7]1[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH2:20][N:21]([CH2:32][C:33]2[C:38]([Cl:39])=[CH:37][CH:36]=[C:35]([O:40][CH3:41])[C:34]=2[F:42])[C@H:22]([CH2:28][N:29]([CH3:31])[CH3:30])[CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:15]=1)=[O:5])C.O.[OH-].[Li+].CO>O1CCCC1>[Cl:39][C:38]1[C:33]([CH2:32][N:21]([CH2:20][C:16]2[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=2)[CH2:13][N:7]2[CH:6]([C:4]([OH:5])=[O:3])[CH2:10][CH2:9][S:8]2(=[O:12])=[O:11])[C@H:22]([CH2:28][N:29]([CH3:30])[CH3:31])[CH2:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[C:34]([F:42])[C:35]([O:40][CH3:41])=[CH:36][CH:37]=1

참가 물질

6

반응물 4

HCID 887MethanolHCID 962WaterHCID 3939Lithium HydroxideHCID 58280466HCID 58280466, 화합물

생성물 1

HCID 58280450HCID 58280450, 화합물

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (0.865 g, 1.4 mmol) was dissolved in tetrahydrofuran (5.6 mL). Water (5.6 mL) and lithium hydroxide (0.050 g, 2.07 mmol) and methanol (1.2 mL) were added. The reaction was stirred at room temperature for 2.5 hours after which the reaction was concentrated under reduced pressure. To the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7) resulting in an emulsion. The reaction was then concentrated to dryness under reduced pressure. The crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2), respectively, 99% (combined yield)).

후처리

  1. concentrationwas concentrated under reduced pressure
  2. additionTo the residue was added dichloromethane and aqueous hydrochloric acid (pH˜7)
  3. customresulting in an emulsion
  4. concentrationThe reaction was then concentrated to dryness under reduced pressure
  5. customThe crude material was purified by supercritical fluid chromatography into the corresponding Epimer 1 and Epimer 2 of 2-(3-{[(6-Chloro-2-fluoro-3-methoxy-benzyl)-((S)-1-dimethylaminomethyl-3,3-dimethyl-butyl)-amino]-methyl}-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid (0.084 g (Epimer 1) and 0.089 g (Epimer 2)
  6. customrespectively, 99% (combined yield))

출처 및 근거

ORD 기록
ord-e014677589b749e5bce43065a1617c9e
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08314250B2

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