Sodium Hydroxide → N-benzyl-2-{[(7S)-11-carboxy-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl]oxy}-N-methylethanaminium chloride

HRID 421950Notes

Reaction equation

HRID 421950 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:27]([O:29]C)=[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]([CH3:45])[CH2:42][CH2:43][Cl:44])[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>[Cl-:44].[CH2:34]([NH+:41]([CH3:45])[CH2:42][CH2:43][O:26][C@H:16]1[CH2:15][N:14]2[C:13]3[CH:12]=[C:11]([C:27]([OH:29])=[O:28])[CH:10]=[CH:9][C:8]=3[C:7]([CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]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

6

Reactant 3

HCID 14798Sodium HydroxideHCID 31967Benzylamine, N-(2-chloroethyl)-N-methyl-, hydrochlorideHCID 66674899methyl (7S)-14-cyclohexyl-7-hydroxy-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Product 1

HCID 86627892N-benzyl-2-{[(7S)-11-carboxy-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocin-7-yl]oxy}-N-methylethanaminium chlorideYield 25%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Procedure

To a suspension of 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 publication WO2006/046030) in toluene (0.05 M), were added 10 eq. of 30% w/w aq. NaOH followed by 0.25 eq. of tetrabutylammonium bromide. After stirring for 30 min, 2.5 eq. of N-benzyl-2-chloro-N-methylethanaminium chloride were added, and the reaction mixture was stirred at 60° C. for 16 h. The reaction mixture was concentrated in vacuo, and the residue purified by RP-HPLC (WATERS XTERRA prep. C18 column, 5um, 19×100 mm. Mobile phase: MeCN/H2O buffered with 0.1% TFA). Fractions containing the pure compound were combined and freeze dried in the presence of HCl to afford the title compound (25%) as a white powder. (ES+) m/z 539 (M+H)+.

Workup

  1. stirringthe reaction mixture was stirred at 60° C. for 16 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe residue purified by RP-HPLC (WATERS XTERRA prep. C18 column, 5um, 19×100 mm. Mobile phase: MeCN/H2O buffered with 0.1% TFA)
  4. additionFractions containing the pure compound
  5. dry with materialfreeze dried in the presence of HCl

Sources & evidence

ORD record
ord-9e38464ea1c540e1b3ca93738b3670e9
Source dataset
uspto-grants-2012_01
Patent number
US08101595B2

Reaction notes

Loading…