Sodium → HCID 22877438, compound

HRID 1379851Notes

Reaction equation

HRID 1379851 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:29])([CH3:28])[C:13]([NH:15][C@@H:16]1[CH2:22][CH2:21][C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[NH:18][C:17]1=[O:27])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na].[C:31]([O:35][C:36]([NH:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:46]1[CH:51]=[CH:50][C:49]([CH2:52]O)=[CH:48][CH:47]=1)=[O:37])([CH3:34])([CH3:33])[CH3:32]>CN(C)C=O>[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:29])([CH3:28])[C:13]([NH:15][C@@H:16]1[CH2:22][CH2:21][C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]([CH2:52][C:49]2[CH:48]=[CH:47][C:46]([C:41]3[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=3[CH2:39][NH:38][C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])=[CH:51][CH:50]=2)[C:17]1=[O:27])=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 5360545SodiumHCID 10739464HCID 10739464, compoundHCID 220084722'-[(t-Butoxycarbonylamino)methyl]-1,1-biphenyl-4-methanol

Product 1

HCID 22877438HCID 22877438, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 819 mg (2.07 mmol) of 2-benzyloxycarbonylamino-2-methyl- N-[2,3,4,5-tetrahydro-2-oxo-1H-benzazepin-3(R)-yl]propanamide (Step A) in 7.0 mL of dry dimethylformamide under nitrogen at 0° C. was added 83 mg (2.1 mmol) of 60% sodium hydrideil dispersion. After stirring for 15 minutes, a solution of 810 mg (2.1 mmol) of 2'-[(t-butoxycarbonylamino)methyl]-1,1'-biphenyl-4-methanol, methanesulfonate ester (Step F) in 2.0 mL of dimethylformamide was added by cannula. The flask which originally contained the methanesulfonate ester was rinsed with 1.0 mL of dimethylformamide which was added to the reaction mixture. After stirring at 0° C. for 15 minutes, the reaction mixture was diluted with 400 mL of ethyl acetate and 50% saturated ammonium chloride. The mixture was transferred to a separatory funnel and the aqueous layer was separated. The organic layer was washed with 100 mL of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The organic layer was dried over magnesium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45) to afford 1.2 g (84%) of the product as a white foam. 1H NMR (200 MHz, CDCl3): δ 1.38 (s, 9H), 1.48 (s, 3H), 1.52 (s, 3H), 1.78 (s, 1H), 2.35-2.70 (m, 3H), 4.18 (d, 6 Hz, 2H), 4.38-4.62 (m, 2H), 4.82 (d, 16 Hz, 1H), 5.05 (s, 2H), 5.25 (d, 16 Hz, 1H), 5.32 (s, 1H), 7.08 (d, 6 Hz, 1H), 7.12-7.43 (m, 18H). FAB-MS: calculated for C41 H46N4O6 690; found 691(M+H).

Workup

  1. washwas rinsed with 1.0 mL of dimethylformamide which
  2. additionwas added to the reaction mixture
  3. stirringAfter stirring at 0° C. for 15 minutes
  4. additionthe reaction mixture was diluted with 400 mL of ethyl acetate and 50% saturated ammonium chloride
  5. customThe mixture was transferred to a separatory funnel
  6. customthe aqueous layer was separated
  7. washThe organic layer was washed with 100 mL of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride
  8. dry with materialThe organic layer was dried over magnesium sulfate
  9. filtrationfiltered
  10. customthe solvent removed under vacuum
  11. customThe residue was purified by flash chromatography on silica gel eluting with ethyl acetate/hexane (55:45)

Sources & evidence

ORD record
ord-027c46caaa9147719b3acdb5bd4ddf73
Source dataset
uspto-grants-1997_09
Patent number
US05672596

Reaction notes

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