Ethanolamine → Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester

HRID 1513936노트

반응식

HRID 1513936 반응식
[F:1][C:2]1[C:3]([S:41][CH3:42])=[C:4]([C:9]2[C:10]([C:24](=[O:40])[C:25]3[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[CH:27][CH:26]=3)=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([O:19][S:20]([CH3:23])(=[O:22])=[O:21])[CH:13]=[CH:12]3)[CH:5]=[C:6]([F:8])[CH:7]=1.C(CN)O.[Cl-].[NH4+]>B.C1COCC1.C1(C(C2C=CC=CC=2)([C@@H]2CCCN2)O)C=CC=CC=1>[F:1][C:2]1[C:3]([S:41][CH3:42])=[C:4]([C:9]2[C:10]([CH:24]([OH:40])[C:25]3[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH2:33][N:34]4[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]4)=[CH:29][CH:30]=3)=[C:11]3[C:16](=[CH:17][CH:18]=2)[CH:15]=[C:14]([O:19][S:20]([CH3:23])(=[O:21])=[O:22])[CH:13]=[CH:12]3)[CH:5]=[C:6]([F:8])[CH:7]=1

참가 물질

7

반응물 3

HCID 700EthanolamineHCID 25517Ammonium ChlorideHCID 57552531Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester

생성물 1

HCID 86626530Methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-{hydroxy-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methyl}-naphthalen-2-yl ester수율 113.7%

시약·촉매·용매 3

HCID 27248992-Pyrrolidinemethanol, alpha,alpha-diphenyl-, (S)-촉매HCID 6331Borane용매HCID 8028Tetrahydrofuran용매2회

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온도
45 °C

실험 절차

Charge a flask with (S)-α,α-diphenyl-2-pyrrolidinemethanol (253 mg, 1.0 mmol) and purge flask with nitrogen. Dilute with 1M borane in THF (43 mL, 43 mmol) and heat to 45° C. under nitrogen. Dissolve methanesulfonic acid 6-(3,5-difluoro-2-methylsulfanyl-phenyl)-5-[4-(2-piperidin-1-yl-ethoxy)-benzoyl]-naphthalen-2-yl ester (6.5 g, 10.6 mmol) in THF (40 mL) and add to the catalyst solution via syringe pump over 2 hours. After complete addition, add ethanolamine (12.8 mL, 212 mmol) slowly and heat at 45° C. for 3 hours. Cool the reaction to room temperature and pour into saturated aqueous ammonium chloride. Extract with methylene chloride, dry over sodium sulfate, filter and concentrate. Purify over silica gel eluting with 3% methanol in methylene chloride to yield 7.4 g (93%) of the title compound (60:40 mixture of diastereomers). LCMS Rt (0.01% heptafluorobutyric acid:1.0% isopropylalcohol:water is mobile phase A and 0.01% heptafluorobutyric acid:1.0% isopropylalcohol:acetonitrile is mobile phase B; gradient method 25 to 95% B, Purity@254 nm)=2.91 and 2.94 mm (100%); mass spectrum (ion spray): m/z=614.2 (M+H).

후처리

  1. custompurge flask with nitrogen
  2. additionAfter complete addition
  3. temperatureheat at 45° C. for 3 hours
  4. temperatureCool
  5. customthe reaction to room temperature
  6. extractionExtract with methylene chloride
  7. dry with materialdry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify over silica gel eluting with 3% methanol in methylene chloride

출처 및 근거

ORD 기록
ord-90342ec7b36b42c78846d36a8caa610a
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217032B2

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