Sodium Hydroxide → HCID 67332907, compound

HRID 1942500Notes

Reaction equation

HRID 1942500 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][N:14]1[C:19]2[CH:20]=[C:21]([C:28]([O:30]C)=[O:29])[C:22]([C:24]([F:27])([F:26])[F:25])=[CH:23][C:18]=2[O:17][C@@:16]([CH3:38])([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:15]1=[O:39])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+]>O1CCOCC1>[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][N:14]1[C:19]2[CH:20]=[C:21]([C:28]([OH:30])=[O:29])[C:22]([C:24]([F:27])([F:26])[F:25])=[CH:23][C:18]=2[O:17][C@@:16]([CH3:38])([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:15]1=[O:39])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 58375914HCID 58375914, compound

Product 1

HCID 67332907HCID 67332907, compoundYield 184.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Methyl (2S)-4-(2-{[(benzyloxy)carbonyl]amino}ethyl)-2-methyl-3-oxo-2-phenyl-7-(trifluoro-methyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylate (1.1117 g) was dissolved in 1,4-dioxane (20 ml), and thereto was added 4N-aqueous sodium hydroxide solution (20 ml), and the mixture was stirred at 50° C. for 6 hours. The mixture was cooled to room temperature, and concentrated under reduced pressure to remove 1,4-dioxane. The residue was diluted with water, and the pH value thereof was adjusted to pH 1 with 3N-hydrochloric acid. The precipitated white solid was collected by filtration to give (2S)-4-(2-{[(benzyloxy)carbonyl]amino}ethyl)-2-methyl-3-oxo-2-phenyl-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-6-carboxylic acid (1.016 2 g). Thus obtained carboxylic acid (717.7 mg) was dissolved in DMF (6 ml), and thereto were added triethylamine (0.75 ml), dimethylaminopyridine (82.0 mg), tert-butyl (3R)-3-(isopropylamino)piperidine-1-carboxylate (1.3400 g), CIP reagent (1.1922 g), and the mixture was stirred at 60° C. under nitrogen atmosphere for 7 hours. To the mixture were additionally added triethylamine (0.57 ml) and CIP reagent (747.7 mg), and the mixture was further stirred at 60° C. for 4 hours. The reaction solution was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give a crude product, which was purified by silica gel chromatography to give the title compound (588.4 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. customto remove 1,4-dioxane
  4. additionThe residue was diluted with water
  5. filtrationThe precipitated white solid was collected by filtration

Sources & evidence

ORD record
ord-0dc761a6587849859e40fc0061a7bc55
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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