Sodium Hydroxide → 3-[(1S)-1-(3,5-difluorophenyl)-2-fluoro-2-methylpropyl]-1-(diphenylmethyl)azetidine

HRID 602695노트

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HRID 602695 반응식
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([CH:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15]2)[C:10]([CH3:13])(O)[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.[FH:37].[OH-].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]([CH:14]2[CH2:17][N:16]([CH:18]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15]2)[C:10]([F:37])([CH3:13])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1

참가 물질

6

반응물 4

HCID 14798Sodium Hydroxide2회HCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 67055316(1S)-1-(3,5-difluorophenyl)-1-[1-(diphenylmethyl)azetidin-3-yl]-2-methylpropan-2-ol

생성물 1

HCID 113273173-[(1S)-1-(3,5-difluorophenyl)-2-fluoro-2-methylpropyl]-1-(diphenylmethyl)azetidine

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
42 °C

실험 절차

To a solution of 5.5 g (13.5 mmole) of (1S)-1-(3,5-difluorophenyl)-1-[1-(diphenylmethyl)azetidin-3-yl]-2-methylpropan-2-ol in 25 mL of CH2Cl2 was added 15 mL of hydrogen fluoride-pyridine and the two-phase mixture was stirred for 15 h at 42° C. Then the reaction mixture was poured to 100 mL of 5N NaOH, 20 mL of aq NaHCO3, 150 mL of CH2Cl2 and 100 mL ice. The pH was adjusted to 8-9 with 2N NaOH. The water layer was extracted with CH2Cl2 (3×1500 mL). The combined organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography with 10% methyl tert-butyl ether-hexane to afford the title compound as a white solid; 1NMR (CDCl3) δ 1.25 (t, J=22 Hz, 6H), 2.33 (t, J=6.5 Hz, 1H), 2.83-2.89 (m, 2H), 3.09-3.11 (m, 2H), 3.60 (m, 1H), 4.30 (s, 1H), 6.68-6.71 (m, 3H), 7.21-7.8 (m, 10H); Mass Spectrum: m/e=410 (M+1)

후처리

  1. extractionThe water layer was extracted with CH2Cl2 (3×1500 mL)
  2. dry with materialThe combined organic layer was dried over Na2SO4
  3. concentrationconcentrated
  4. customThe residue was purified by silica gel chromatography with 10% methyl tert-butyl ether-hexane

출처 및 근거

ORD 기록
ord-ff26a62f538a4481bc57474ec27166fe
출처 데이터셋
uspto-grants-2011_03
특허 번호
US07906503B2

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