Benzyl Bromide → 3-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-(phenylmethyl)-1H-1-benzazepin-3(R)-yl]-butanamide

HRID 1591427Notes

Reaction equation

HRID 1591427 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:30])([CH3:29])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[NH:19][C:18]1=[O:28])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(OCC)(=O)C>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:30])([CH3:29])[CH2:13][C:14]([NH:16][C@@H:17]1[CH2:23][CH2:22][C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]=2[N:19]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:18]1=[O:28])=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 7498Benzyl BromideHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 105735633-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]butanamide

Product 1

HCID 186514633-Benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1-(phenylmethyl)-1H-1-benzazepin-3(R)-yl]-butanamideYield 898%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 40 mg (0.098 mmol) of 3-benzyloxycarbonylamino-3-methyl-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]-butanamide (Example 1, Step F) in 0.5 mL of dry dimethylformamide at room temperature under nitrogen was added 5 mg of 60% sodium hydride oil dispersion (3 mg NaH, 0.13 mmol, 1.3 eq). After 5 minutes, 0.013 mL of benzyl bromide (19 mg, 0.11 mmol, 1.1 eq) was added and the mixture stirred for 1 hour at room temperature, then added to 20 mL of ethyl acetate and washed with water (2×) and brine. The organic layer was removed, dried over magnesium sulfate, filtered and solvents removed under vacuum. The residue was purified by medium pressure liquid chromatography on silica, eluting with ethyl acetate/hexane (1:1) to afford 44 mg (0.88 mmol, 90%) of product. 1H NMR (200 MHz, CDCl3): 1.37 (s,3H), 1.38 (s,3H), 1.73 (m,1H), 2.3-2.6 (m,5H), 4.48 (m,1H), 4.80 (d,15 Hz,1H), 5.07 (br s,2H), 5.23 (d,15 Hz,1H), 5.62 (br s,1H), 6.67 (br d,7 Hz,1H), 7.1-7.4 (m,14H). FAB-MS: calculated for C30H33N3O4 499; found 500 (M+H,100%).

Workup

  1. washwashed with water (2×) and brine
  2. customThe organic layer was removed
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customsolvents removed under vacuum
  6. customThe residue was purified by medium pressure liquid chromatography on silica
  7. washeluting with ethyl acetate/hexane (1:1)

Sources & evidence

ORD record
ord-aa7a7341363d46529ef38db0342f7a29
Source dataset
uspto-grants-1993_04
Patent number
US05206235

Reaction notes

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