Lithium hydroxide, monohydrate → HCID 90037019, compound

HRID 1055455Notes

Reaction equation

HRID 1055455 reaction equation
O[Li].O.[Br:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([CH2:15][N:16]1[C:22](=[O:23])[C@@H:21]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20][O:19][C:18]3[C:32]([C:36]([O:38]C)=[O:37])=[CH:33][CH:34]=[CH:35][C:17]1=3)=[C:10]([O:40][CH3:41])[CH:9]=[CH:8]2>CO>[Br:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([CH2:15][N:16]1[C:22](=[O:23])[C@@H:21]([NH:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:20][O:19][C:18]3[C:32]([C:36]([OH:38])=[O:37])=[CH:33][CH:34]=[CH:35][C:17]1=3)=[C:10]([O:40][CH3:41])[CH:9]=[CH:8]2

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 90037313HCID 90037313, compound

Product 1

HCID 90037019HCID 90037019, compoundYield 90.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
47.5 °C

Procedure

A 0.1 M aqueous solution of LiOH.H2O (5.98 mL, 598 μmol, Eq: 1.00) was added to a solution of (S)-methyl 5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-3-(tert-butoxycarbonylamino)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylate (0.35 g, 598 μmol, Eq: 1.00) in MeOH (20 mL) and the mixture was warmed to 45-50° C. After 7 h, the MeOH was removed in vacuo and the mixture diluted with sat. NaHCO3 then extracted with EtOAc. The aqueous mixture was cooled to 0° C., acidifed to pH 3.0 with 3 N HCl and extracted with EtOAc. The combined organic extracts were washed with brine and concentrated a to give a material that was purified by silica gel chromatography to afford (S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-3-(tert-butoxycarbonylamino)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepine-9-carboxylic acid (310 mg, 90%) as a white foam.

Workup

  1. customthe MeOH was removed in vacuo
  2. additionthe mixture diluted with sat. NaHCO3
  3. extractionthen extracted with EtOAc
  4. temperatureThe aqueous mixture was cooled to 0° C.
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with brine
  7. concentrationconcentrated
  8. customa to give a material that
  9. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-7fee34ac76884e32ac5a53e22da5019d
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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