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 1714037Notes

Reaction equation

HRID 1714037 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.[H-].[Na+].Cl[CH2:30][C:31]([CH2:33]Cl)=[CH2:32]>CN(C=O)C.CCOC(C)=O>[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][CH2:33][C:31](=[CH2:30])[CH2:32]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 158593-Chloro-2-chloromethyl-1-propeneHCID 24758Sodium hydrideHCID 11995228Methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate

Product 1

HCID 66674413methyl 14-cyclohexyl-7-methylene-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of methyl 3-cyclohexyl-2-(2-hydroxyphenyl)-1H-indole-6-carboxylate (prepared as described in example 9, step 1) in dry DMF (0.06 M) was added NaH (2.5 eq., 60% suspension in mineral oil). After 30 min, 3-chloro-2-(chloromethyl)prop-1-ene (1.2 eq.) was added dropwise via syringe and the solution stirred at RT for 60 min. The reaction mixture was diluted with EtOAc and washed with 1N aqueous HCl and with brine, dried (Na2SO4) and evaporated. The crude residue was purified by flash chromatography (10:1 PE/EtOAc), affording the pure methyl 14-cyclohexyl-7-methylene-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (70%) as light yellow foam; MS (ES+) m/z 402 (M+H)+.

Workup

  1. washwashed with 1N aqueous HCl and with brine
  2. dry with materialdried (Na2SO4)
  3. customevaporated
  4. customThe crude residue was purified by flash chromatography (10:1 PE/EtOAc)

Sources & evidence

ORD record
ord-f6a89467e0c64975888a8ee6a25286d7
Source dataset
uspto-grants-2010_09
Patent number
US07795247B2

Reaction notes

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