Acetonitrile → N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide

HRID 1610720Notes

Reaction equation

HRID 1610720 reaction equation
[NH2:1][CH:2]([CH2:12]CC1C=CC(C(C)(C)C)=CC=1)[CH:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=1)[OH:4].[C:24]1([C:35]([OH:37])=O)[CH:25]=[CH:26][CH:27]=[C:28]2[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=12.O.ON1[C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2N=N1.Cl.C(N=C=N[CH2:55][CH2:56][CH2:57]N(C)C)C.[C:61](#N)C>C(OCC)(=O)C>[C:56]([C:43]1[CH:48]=[CH:47][C:46]([CH2:12][CH:2]([NH:1][C:35]([C:24]2[CH:25]=[CH:26][CH:27]=[C:28]3[CH2:34][CH2:33][CH2:32][CH:31]=[CH:30][C:29]=23)=[O:37])[CH:3]([C:5]2[CH:10]=[CH:9][C:8]([F:11])=[CH:7][CH:6]=2)[OH:4])=[CH:45][CH:44]=1)([CH3:57])([CH3:61])[CH3:55]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22261419(1RS,2RS)-2-amino-3-[4-(tert-butyl)benzyl]-1-(4-fluorophenyl)propan-1-olHCID 222620106,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid

Product 1

HCID 22262326N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamideYield 67%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (1RS,2RS)-2-amino-3-[4-(tert-butyl)benzyl]-1-(4-fluorophenyl)propan-1-ol (0.41 g, 1.36 mmol) in acetonitrile (10 ml) were added 6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxylic acid (0.20 g, 1.05 mmol) and 1-hydroxybenzotriazole monohydrate (0.16 g, 1.05 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.20 g, 1.05 mmol) was finally added. The mixture was stirred at room temperature for 3 days. The mixture was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1, 2:1). Recrystallization (hexane-ethyl acetate) gave N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-6,7-dihydro-5H-benzo[a]cycloheptene-1-carboxamide (0.43 g, 67%) as colorless crystals.

Workup

  1. additionwas finally added
  2. washwashed with saturated aqueous sodium hydrogen carbonate solution, water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=5:1, 2:1)
  7. customRecrystallization (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-663e705dae894f2f896ac1a54129cd0f
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

Loading…