Potassium Carbonate → 6-Fluoro-4-[3-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]-2-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 1017039노트

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HRID 1017039 반응식
F[C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:30])([F:29])[CH:26]([F:28])[F:27])[CH:19]=1)[CH2:10][CH:11]([OH:16])[C:12]([F:15])([F:14])[F:13].C([O-])([O-])=O.[K+].[K+]>CN(C)C=O.O>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[O:16][CH:11]([C:12]([F:13])([F:14])[F:15])[CH2:10][N:9]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][C:25]([F:29])([F:30])[CH:26]([F:27])[F:28])[CH:19]=3)[C:3]=2[CH:4]=1

참가 물질

5

반응물 2

HCID 11430Potassium CarbonateHCID 235060713-[(2,5-Difluorophenyl)[[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

생성물 1

HCID 108952136-Fluoro-4-[3-(1,1,2,2-tetrafluoro-ethoxy)-benzyl]-2-trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine수율 48%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

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온도
145 °C

실험 절차

The 3-[(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol (200 mg, 0.45 mmol) product from EX-661B was dissolved in anhydrous dimethylformamide (20 mL), and powdered K2CO3 (180 mg) was added. The mixture was stirred and heated to 145° C. for 15 h. The mixture was diluted with water (60 mL) and extracted into ether (2×40 mL), which was washed with brine and water. The ether solution was dried over anhydrous MgSO4, and the ether was removed in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:15) to give 86.9 mg (48%) of the desired 6-fluoro-3,4-dihydro-4-[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-2-(tri-fluoromethyl)-2H-1,4benzoxazine product as a yellow oil, 98% pure by HPLC analysis. 1H NMR (CDCl3) δ7.39 (t, 1H), 7.17 (m, 3H), 6.88 (m, 1H), 6.41 (m, 2H), 5.92 (tt, 1H), 4.54 (m, 1H), 4.45 (s, 2H), 3.44 (m, 2H). 19H NMR (CDCl3) δ−77.7 (d, 3F), −88.6 (m, 2F), −120.28 (m, IF), −137.2 (dt, 2F). HRMS calcd. for C18H13F8NO2: 428.0899 [M+H]+, found: 428.0910.

후처리

  1. extractionextracted into ether (2×40 mL), which
  2. washwas washed with brine and water
  3. dry with materialThe ether solution was dried over anhydrous MgSO4
  4. customthe ether was removed in vacuo
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:15)

출처 및 근거

ORD 기록
ord-f55fa12608944f87806a4563afd345ea
출처 데이터셋
uspto-grants-2002_11
특허 번호
US06476057B1

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