Triethylamine → Rac-2-cyclopentyloxy-2-(3,4-dichloro-phenyl)-n-pyridin-2-yl-acetamide

HRID 397191Notes

Reaction equation

HRID 397191 reaction equation
[CH:1]1([O:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.ClC1C=C(Cl)C=C(Cl)C=1C(Cl)=O.[NH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=1>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1.O>[CH:1]1([O:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][N:40]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 104392-AminopyridineHCID 27337032,4,6-Trichlorobenzoyl chlorideHCID 12044174Rac-cyclopentyloxy-(3,4-dichloro-phenyl)-acetic acid

Product 1

HCID 9947241Rac-2-cyclopentyloxy-2-(3,4-dichloro-phenyl)-n-pyridin-2-yl-acetamideYield 77.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of rac-cyclopentyloxy-(3,4-dichloro-phenyl)-acetic acid (from Example 1, 50 mg, 0.17 mmol) and triethylamine (0.07 mL, 0.52 mmol) in toluene (5 mL), previously cooled to 0° C. was treated with 2,4,6-trichlorobenzoyl chloride (0.03 mL, 0.19 mmol) and the mixture was stirred at 0° C. After 1 h, 2-aminopyridine (20 mg, 0.21 mmol) and 4-dimethylaminopyridine (5 mg, 0.035 mmol) were added and the stirring was continued for 1 h at 0° C. The reaction was checked for completion, then it was diluted with water (10 mL) and extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The product was purified by chromatography (Biotage Flash 12M column, 80/20 hexanes/ethyl acetate) to give rac-2-cyclopentyloxy-2-(3,4-dichloro-phenyl)-N-pyridin-2-yl-acetamide (48 mg, 76% yield) as a white foam: EI-HRMS m/e calculated for C18H18N2O2Cl2 (M+) 364.0745, found 364.0746.

Workup

  1. waitthe stirring was continued for 1 h at 0° C
  2. extractionextracted with dichloromethane (3×10 mL)
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe product was purified by chromatography (Biotage Flash 12M column, 80/20 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-3e343e133930445fb76d5cf9aaf1bcec
Source dataset
uspto-grants-2003_08
Patent number
US06608218B2

Reaction notes

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