Lithium hydroxide, monohydrate → (7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acid

HRID 498995Notes

Reaction equation

HRID 498995 reaction equation
O.[OH-].[Li+].[C:4]([O:8][C:9]([NH:11][CH2:12][CH2:13][N:14]([CH3:44])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([O:38]C)=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>CO.C1COCC1.O>[C:4]([O:8][C:9]([NH:11][CH2:12][CH2:13][N:14]([CH3:44])[C@@H:15]1[CH2:22][N:21]2[C:23]3[CH:24]=[C:25]([C:36]([OH:38])=[O:37])[CH:26]=[CH:27][C:28]=3[C:29]([CH:30]3[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35]3)=[C:20]2[C:19]2[CH:40]=[CH:41][CH:42]=[CH:43][C:18]=2[O:17][CH2:16]1)=[O:10])([CH3:7])([CH3:6])[CH3:5]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrate2×HCID 53381224methyl(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate

Product 1

HCID 66674687(7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylic acidYield 98%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
60 °C

Procedure

Lithium hydroxide monohydrate (4.4 eq) was added to a solution of methyl (7R)-7-[{2-[(tert-butoxycarbonyl)amino]ethyl}(methyl)amino]-14-cyclohexyl-7,8-dihydro-6H-indolo[1,2-e][1,5]benzoxazocine-11-carboxylate (0.02 M) in MeOH/THF/H2O (1/1/1). The reaction was heated at 60° C. for 4 h prior to introducing further lithium hydroxide monohydrate (5 eq) and continuing heating for 2 h. The reaction was allowed to cool to RT, and the solvent volume reduced in vacuo. The residue was partitioned between 1N HCl (aq) and EtOAc, extracting the aqueous fraction a further two times with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford the product as an off white foam (98%). (ES+) m/z 548 (M+H)+

Workup

  1. temperaturecontinuing heating for 2 h
  2. temperatureto cool to RT
  3. customThe residue was partitioned between 1N HCl (aq) and EtOAc
  4. extractionextracting the aqueous fraction a further two times with EtOAc
  5. washThe combined organics were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5b5941e1260049bbb1a77f6896a3cdce
Source dataset
uspto-grants-2010_08
Patent number
US07767660B2

Reaction notes

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