4-Methylmorpholine → N-[3-(4-Chlorophenyl)-2-phenyl-1-methylpropyl]-1-phenylcyclopentanecarboxamide

HRID 30389

Reaction equation

HRID 30389 reaction equation
[C:1]1([C:7]2([C:12]([OH:14])=O)[CH2:11][CH2:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.Cl.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][CH:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH:31]([NH2:33])[CH3:32])=[CH:25][CH:24]=1.CN1CCOCC1>C(Cl)Cl.CN(C)C=O>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([CH2:29][CH:30]([C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[CH:31]([NH:33][C:12]([C:7]2([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:8][CH2:9][CH2:10][CH2:11]2)=[O:14])[CH3:32])=[CH:27][CH:28]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 65578Oxalyl chlorideHCID 661671-Phenylcyclopentanecarboxylic acidHCID 22270502N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochloride

Product 1

HCID 10127240N-[3-(4-Chlorophenyl)-2-phenyl-1-methylpropyl]-1-phenylcyclopentanecarboxamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of phenylcyclopentanecarboxylic acid (Aldrich, 23 mg, 0.12 mmol) in methylene chloride (1 mL) at 0° C. was added a drop of dimethylformamide and oxalyl chloride (0.025 mL, 0.29 mmol). After stirring at room temperature for 1 h, the reaction mixture was concentrated on a rotary evaporator and dried under vacuum, and the resulting crude acyl chloride was used without further purification. The crude acyl chloride was dissolved in 1 mL of methylene chloride and was added to a suspension of N-[3-(4-chlorophenyl)-2-phenyl-1-methylpropyl]-amine hydrochloride (Reference Example 2) (diastereomer α, 30 mg, 0.10 mmol) and N-methylmorpholine (0.053 mL, 0.48 mmol) in 1 mL of methylene chloride. After stirring at room temperature overnight, the reaction mixture was loaded onto a silica gel column, which was eluted with 10% ethyl acetate to give the title compound. 1H NMR (400 MHz, CD3OD): δ 7.45 (d, 2H), 7.35-7.08 (m, 6 H), 6.97 (d, 2H) 6.90 (d, 2H), 6.59 (d, 2H), 4.19 (m, 1H), 2.74-2.45 (m, 5), 2.12-1.65 (m, 6H), 0.79 (d, 3H). LC-MS: m/e 432 (M+H)+ (4.4 min).

Workup

  1. concentrationthe reaction mixture was concentrated on a rotary evaporator
  2. customdried under vacuum
  3. customthe resulting crude acyl chloride was used without further purification
  4. dissolutionThe crude acyl chloride was dissolved in 1 mL of methylene chloride
  5. stirringAfter stirring at room temperature overnight
  6. washwas eluted with 10% ethyl acetate

Sources & evidence

ORD record
ord-0ed47ef411b14354ae68eda75176e24c
Source dataset
uspto-grants-2008_09
Patent number
US07423067B2

Linked notes

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