Hydrochloric Acid → 2-Methyl-2-{3-[1-(4-trifluoromethyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid benzyl ester

HRID 1269516Notes

Reaction equation

HRID 1269516 reaction equation
[F:1][C:2]([F:12])([F:11])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH2:8])=[CH:5][CH:4]=1.[C:13](N1C=CN=C1)(N1C=CN=C1)=[O:14].[CH2:25]([O:32][C:33](=[O:50])[C:34]([CH3:49])([O:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH:43]2[CH2:48][CH2:47][CH2:46][NH:45][CH2:44]2)[CH:38]=1)[CH3:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.Cl>C1(C)C=CC=CC=1.O>[CH2:25]([O:32][C:33](=[O:50])[C:34]([CH3:35])([O:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH:43]2[CH2:48][CH2:47][CH2:46][N:45]([C:13](=[O:14])[NH:8][CH2:7][C:6]3[CH:9]=[CH:10][C:3]([C:2]([F:11])([F:12])[F:1])=[CH:4][CH:5]=3)[CH2:44]2)[CH:38]=1)[CH3:49])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 768044-(Trifluoromethyl)benzylamineHCID 688839562-Methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester

Product 1

HCID 688838662-Methyl-2-{3-[1-(4-trifluoromethyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid benzyl esterYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

To a solution of 4-trifluoromethylbenzyl amine (170 mL, 1.19 mmol) in 5 mL toluene was added 1,1′-carbonyldiimidazole (193 mg, 1.19 mmol). This solution was stirred 18 h at ambient temperature. 2-methyl-2-(3-piperidin-3-yl-phenoxy)-propionic acid benzyl ester (Preparation 2, Method C; 421 mg, 1.19 mmol) was added in 5 mL toluene and the resultant solution was stirred 18 h at ambient temperature. The reaction was diluted with water (100 mL), acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resultant oil was flash chromatographed with 35% ethyl acetate/hexanes to yield 473 mg (72%) of the desired 2-methyl-2-{3-[1-(4-trifluoromethyl-benzylcarbamoyl)-piperidin-3-yl]-phenoxy}-propionic acid benzyl ester as a clear oil.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customchromatographed with 35% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-4d4a620876e04d24886ca96448eec95d
Source dataset
uspto-grants-2007_04
Patent number
US07199243B2

Reaction notes

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