Cesium fluoride → methyl (7R)-7-[(tert-butoxycarbonyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 1669394노트

반응식

HRID 1669394 반응식
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[OH:26])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+].[N+](C1C=CC(S(O[CH2:42][C@H:43]2[CH2:45][N:44]2[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])(=O)=O)=CC=1)([O-])=O.CC([O-])(C)C.[K+]>CN(C=O)C>[C:49]([O:48][C:46]([NH:44][C@@H:43]1[CH2:45][N:9]2[C:10]3[CH:11]=[C:12]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:14][C:15]=3[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[C:8]2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH2:42]1)=[O:47])([CH3:52])([CH3:51])[CH3:50]

참가 물질

6

반응물 4

HCID 25953Cesium fluorideHCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylateHCID 23665647Potassium tert-butoxideHCID 53381222tert-butyl (2R)-2-({[(4-nitrophenyl)sulfonyl]oxy}methyl)aziridine-1-carboxylate

생성물 1

HCID 53381223methyl (7R)-7-[(tert-butoxycarbonyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate수율 85%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

A solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in published International patent application WO2006/046030) (0.15 M) in DMF was treated with CsF (4 eq) in one portion; the resulting mixture was stirred for 20 min at RT then treated via dropping funnel over 30 min with a solution of tert-butyl (2R)-2-({[(4-nitrophenyl)sulfonyl]oxy}methyl)aziridine-1-carboxylate (1.3 eq) in DMF (0.5 M). The resulting solution was stirred at RT overnight. The reaction mixture was then placed into an ice bath and powdered KOtBu (1.4 eq) added slowly to the reaction mixture. After 1.5 h, the reaction was quenched with sat. aq. NH4Cl and extracted into EtOAc. The combined organic layers were washed with water and brine, before being dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by FC (PE/EtOAc 8:2) affording the product as an off-white foam (85%). (ES+) m/z 505 (M+H)+.

후처리

  1. additionthen treated
  2. customover 30 min
  3. stirringThe resulting solution was stirred at RT overnight
  4. customThe reaction mixture was then placed into an ice bath
  5. waitAfter 1.5 h
  6. customthe reaction was quenched with sat. aq. NH4Cl
  7. extractionextracted into EtOAc
  8. washThe combined organic layers were washed with water and brine
  9. dry with materialbefore being dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by FC (PE/EtOAc 8:2)

출처 및 근거

ORD 기록
ord-f6c156f4a85147bc93910aa5193dc45c
출처 데이터셋
uspto-grants-2011_08
특허 번호
US07989438B2

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