Dimethylformamide → N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-5-chloro-1-naphthamide

HRID 1610736Notes

Reaction equation

HRID 1610736 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].[Cl:24][C:25]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:26]=1[CH:27]=[CH:28][CH:29]=[C:30]2[C:35]([OH:37])=O.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.[CH3:61]N(C)C=O>C(OCC)(=O)C>[C:56]([C:43]1[CH:48]=[CH:47][C:46]([CH2:12][CH:2]([NH:1][C:35]([C:30]2[C:31]3[C:26](=[C:25]([Cl:24])[CH:34]=[CH:33][CH:32]=3)[CH:27]=[CH:28][CH:29]=2)=[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 6228DimethylformamideHCID 9370575-Chloro-1-naphthoic acidHCID 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-ol

Product 1

HCID 22262155N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-5-chloro-1-naphthamideYield 57%

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 (0.34 g, 1.1 mmol) in N,N-dimethylformamide (10 ml) were added 5-chloronaphthalene-1-carboxylic acid (208 mg, 1.0 mmol) and 1-hydroxybenzotriazole monohydrate (170 mg, 1.1 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (210 mg, 1.1 mmol) was finally added. The mixture was stirred overnight at room temperature. 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=2:1) and recrystallization (hexane-ethyl acetate) to give N-[(1RS,2SR)-1-(4-tert-butylbenzyl)-2-(4-fluorophenyl)-2-hydroxyethyl]-5-chloro-1-naphthamide (265 mg, 57%) 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=2:1) and recrystallization (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-f1368f6bb283446fa1dda3b59a8b2cab
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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