Benzyl Bromide → HCID 67330354, compound

HRID 1942507Notes

Reaction equation

HRID 1942507 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]([N:30]([C@@H:34]3[CH2:39][CH2:38][CH2:37][N:36]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:35]3)[CH:31]([CH3:33])[CH3:32])=[O:29])[C:22]([C:24]([F:27])([F:26])[F:25])=[CH:23][C:18]=2[O:17][C:16]([CH3:52])([C:47]([O:49]CC)=[O:48])[C:15]1=[O:53])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:54](Br)[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1.[H-].[Na+].[OH-].[Na+].S([O-])(O)(=O)=O.[K+]>CN(C)C(=O)C.O1CCCC1>[CH2:54]([N:11]([C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[CH2:12][CH2:13][N:14]1[C:19]2[CH:20]=[C:21]([C:28]([N:30]([C@@H:34]3[CH2:39][CH2:38][CH2:37][N:36]([C:40]([O:42][C:43]([CH3:46])([CH3:44])[CH3:45])=[O:41])[CH2:35]3)[CH:31]([CH3:33])[CH3:32])=[O:29])[C:22]([C:24]([F:26])([F:27])[F:25])=[CH:23][C:18]=2[O:17][C:16]([CH3:52])([C:47]([OH:49])=[O:48])[C:15]1=[O:53])[C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1

Participants

8

Reactant 5

HCID 7498Benzyl BromideHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 67330115HCID 67330115, compound

Product 1

HCID 67330354HCID 67330354, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of ethyl 4-(2-{[(benzyloxy)carbonyl]amino}ethyl)-6-{[[(3R)-1-(tert-butoxycarbonyl)piperidin-3-yl](isopropyl)amino]carbonyl}-2-methyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate (1.00 g) in N,N-dimethylacetamide (2.7 ml) was added at 0° C. benzyl bromide (0.794 ml), and sodium hydride (193 mg), and the mixture was stirred for one hour. To the reaction solution were added 2N-aqueous sodium hydroxide solution (5.36 ml) and tetrahydrofuran (5.0 ml), and the mixture was stirred at room temperature for one hour. To the reaction solution was added a 5% aqueous potassium hydrogen sulfate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform /methanol=100/3, containing 5% acetic acid) to give the title compound (0.800 g).

Workup

  1. stirringthe mixture was stirred at room temperature for one hour
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (chloroform /methanol=100/3, containing 5% acetic acid)

Sources & evidence

ORD record
ord-6b43720b9f0149b08fa3607aa809dd86
Source dataset
uspto-grants-2013_03
Patent number
US08389511B2

Reaction notes

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