3-Chloro-2-chloromethyl-1-propene → methyl 14-cyclohexyl-7-methylene-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 1669440Notes

Reaction equation

HRID 1669440 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.[CH3:27][C:28]([O-])([CH3:30])[CH3:29].[K+].ClCC(CCl)=C>CN(C=O)C>[CH:1]1([C:7]2[C:15]3[CH:14]=[CH:13][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:10]=3[N:9]3[C:8]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[O:26][CH2:30][C:28](=[CH2:27])[CH2:29]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 158593-Chloro-2-chloromethyl-1-propeneHCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylateHCID 23665647Potassium tert-butoxide

Product 1

HCID 66674413methyl 14-cyclohexyl-7-methylene-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in International patent application WO2006/046030) (0.12 M) in DMF was treated with KOtBu (2.1 eq) in one portion; the resulting mixture was stirred for 30 min at RT then treated dropwise with 3-chloro-2-(chloromethyl)prop-1-ene (1.1 eq). The resulting solution was stirred at RT overnight before being quenched by addition of HCl (1N) and extracted into EtOAc. The combined organic layers were washed with sat. aq. NaHCO3 and brine, before being dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by FC (PE/EtOAc 85:15) affording the product as a yellow oil (97%). (ES+) m/z 402 (M+H)+.

Workup

  1. stirringThe resulting solution was stirred at RT overnight
  2. custombefore being quenched by addition of HCl (1N)
  3. extractionextracted into EtOAc
  4. washThe combined organic layers were washed with sat. aq. NaHCO3 and brine
  5. dry with materialbefore being dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by FC (PE/EtOAc 85:15)

Sources & evidence

ORD record
ord-50b144994479447e865237276f33ec45
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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