Diisopropylethylamine → N-{(2-R)-3-[4-(3,4-Dichlorophenoxy)piperidin-1-yl]-2-hydroxypropyl}-2-(methylsulfonyl)benzamide

HRID 2233398Notes

Reaction equation

HRID 2233398 reaction equation
[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)(=[O:4])=[O:3].[NH2:14][CH2:15][C@@H:16]([OH:33])[CH2:17][N:18]1[CH2:23][CH2:22][CH:21]([O:24][C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[C:27]([Cl:32])[CH:26]=2)[CH2:20][CH2:19]1.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Cl:32][C:27]1[CH:26]=[C:25]([CH:30]=[CH:29][C:28]=1[Cl:31])[O:24][CH:21]1[CH2:20][CH2:19][N:18]([CH2:17][C@H:16]([OH:33])[CH2:15][NH:14][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[S:2]([CH3:1])(=[O:3])=[O:4])[CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2843422-Methanesulfonylbenzoic acidHCID 516892Sodium BicarbonateHCID 11151315(2R)-1-amino-3-[4-(3,4-dichlorophenoxy)piperidin-1-yl)propan-2-ol

Product 1

HCID 59296109N-{(2-R)-3-[4-(3,4-Dichlorophenoxy)piperidin-1-yl]-2-hydroxypropyl}-2-(methylsulfonyl)benzamideYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2-(methylsulphonyl)benzoic acid (0.063 g), (2R)-1-amino-3-[4-(3,4-dichlorophenoxy)piperidin-1-yl]propan-2-ol (0.1 g) and N,N-diisopropylethylamine (0.1 ml) in dry dimethylformamide (3 ml) was cooled to 0° C. with stirring. 2-(1H-9-Azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.13 g) was added and the mixture was stirred at 0° C. for 1-2 h. Saturated sodium bicarbonate solution (10 ml) was added. The mixture was extracted with ethyl acetate. The organic layer was separated and washed with brine and dried over sodium sulphate. The mixture was filtered and the solvent was evaporated. The resulting oil was purified by normal phase chromatography using methanol/dichloromethane as eluent, and by reverse phase HPLC using acetonitrile and 0.1% aqueous ammonium acetate as eluent, to give the title compound as a white solid (0.055 g).

Workup

  1. stirringthe mixture was stirred at 0° C. for 1-2 h
  2. extractionThe mixture was extracted with ethyl acetate
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried over sodium sulphate
  6. filtrationThe mixture was filtered
  7. customthe solvent was evaporated
  8. customThe resulting oil was purified by normal phase chromatography

Sources & evidence

ORD record
ord-2041d59b8f4248ed8349d853ca2af3ae
Source dataset
uspto-grants-2010_05
Patent number
US07709500B2

Reaction notes

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