Diethyl Ether → Azepane-1-carboxylic acid {1-[2-(4-benzyloxy-phenyl)-1-tert-butoxymethyl-ethylcarbamoyl]-3-methyl-butyl}-amide

HRID 278877Notes

Reaction equation

HRID 278877 reaction equation
[N:1]1([C:8]([NH:10][C@@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([OH:14])=O)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CN1CCOCC1.[CH2:26]([O:33][C:34]1[CH:48]=[CH:47][C:37]([CH2:38][C@H:39]([NH2:46])[CH2:40][O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[CH:36][CH:35]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(OCC)C>CN(C)C=O>[CH2:26]([O:33][C:34]1[CH:35]=[CH:36][C:37]([CH2:38][CH:39]([NH:46][C:12]([CH:11]([NH:10][C:8]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[O:9])[CH2:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH2:40][O:41][C:42]([CH3:44])([CH3:43])[CH3:45])=[CH:47][CH:48]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 79724-MethylmorpholineHCID 7530182(2S)-2-(azepane-1-carbonylamino)-4-methylpentanoic acidHCID 12040965(s)-1-(4-Benzyloxy-benzyl)-2-tert-butoxy-ethylamine

Product 1

HCID 18711790Azepane-1-carboxylic acid {1-[2-(4-benzyloxy-phenyl)-1-tert-butoxymethyl-ethylcarbamoyl]-3-methyl-butyl}-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
3 °C

Procedure

A 3° C. solution of 106 mg (0.41 mmol) (S)-2-[(azepane-1-carbonyl)-amino]-4-methyl-pentanoic acid (Example 1, Step B) and 0.137 mL (0.41 mmol) 4-methylmorpholine in 2 mL N,N-dimethylformamide was treated with 165 mg (0.44 mmol) O-benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)uranium hexafluorophosphate (Novabiochem, La Jolla, Calif.), and stirred for 30 minutes, at which time a solution of (S)-1-(4-benzyloxy-benzyl)-2-tert-butoxy-ethylamine in 3 mL dimethylformamide was added and the mixture stirred at 3° C. for 40 minutes. The clear solution was poured into 15 mL diethyl ether and washed successively with 15 mL of each of the following: 5% aqueous HCl, brine, saturated aqueous NaHCO3, brine (twice) then dried over anhydrous magnesium sulfate. The solvent was removed in vacuo affording 180 mg of white solid, which was recrystallized from hexane to give 116 mg (51%) of the title compound as a white solid; mp 98-99° C.

Workup

  1. additionwas added
  2. washwashed successively with 15 mL of each of the following: 5% aqueous HCl, brine, saturated aqueous NaHCO3, brine (twice)
  3. dry with materialthen dried over anhydrous magnesium sulfate
  4. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ecfb45e40f6144f195f45fa8ae1a7811
Source dataset
uspto-grants-2002_03
Patent number
US06362174B1

Reaction notes

Loading…