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

HRID 1669394Notes

Reaction equation

HRID 1669394 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 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)+.

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 8:2)

Sources & evidence

ORD record
ord-f6c156f4a85147bc93910aa5193dc45c
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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