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

HRID 498992Notes

Reaction equation

HRID 498992 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in 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 80:20) affording the product as an off-white foam (85%). (ES+) m/z 505 (M+H)+

Workup

  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 80:20)

Sources & evidence

ORD record
ord-ce5f74c39cfb4f31b69b3dc418712038
Source dataset
uspto-grants-2010_08
Patent number
US07767660B2

Reaction notes

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