Sodium Hydroxide → methyl (7S)-7-[(1-benzylpyrrolidin-2-yl)methoxy]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

HRID 1669449Notes

Reaction equation

HRID 1669449 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:27]([O:29][CH3:30])=[O:28])=[CH:12][C:13]=3[N:14]3[C:21]=2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17][C@@H:16]([OH:26])[CH2:15]3)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[Cl-].[CH2:34]([NH+:41]1[CH2:45][CH2:44][CH2:43][CH:42]1[CH2:46]Cl)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>[CH2:34]([N:41]1[CH2:45][CH2:44][CH2:43][CH:42]1[CH2:46][O:26][C@H:16]1[CH2:15][N:14]2[C:13]3[CH:12]=[C:11]([C:27]([O:29][CH3:30])=[O:28])[CH:10]=[CH:9][C:8]=3[C:7]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[C:21]2[C:20]2[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=2[O:18][CH2:17]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 66674899methyl (7S)-14-cyclohexyl-7-hydroxy-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateHCID 866279031-Benzyl-2-(chloromethyl)pyrrolidinium chloride

Product 1

HCID 67344945methyl (7S)-7-[(1-benzylpyrrolidin-2-yl)methoxy]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Methyl (7S)-14-cyclohexyl-7-hydroxy-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (prepared as described in International patent application WO2006/046030) in toluene (0.17 M) was treated with 30% NaOH (aq) (10 eq) and tetrabutylammonium bromide (0.25 eq). The solution was stirred at RT for 30 min, then 1-benzyl-2-(chloromethyl)pyrrolidinium chloride (2.5 eq) was added to the solution and the resulting mixture was stirred at 60° C. over night. Toluene was eliminated in vacuo; the residue was taken up in EtOAc and washed with 1 N HCl (aq), brine, before being dried (Na2SO4), filtered and concentrated in vacuo. The crude material was purified by FC (PE/EtOAc 50:50+1% NEt3) to afford the product (80%). (ES+) m/z 579 (M+H)+

Workup

  1. stirringthe resulting mixture was stirred at 60° C. over night
  2. washwashed with 1 N HCl (aq), brine
  3. dry with materialbefore being dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by FC (PE/EtOAc 50:50+1% NEt3)

Sources & evidence

ORD record
ord-dd6b5182eece4c71b16dfad9420ccda1
Source dataset
uspto-grants-2011_08
Patent number
US07989438B2

Reaction notes

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