3,5-Bis(trifluoromethyl)benzoic acid → 1-tert-Butoxycarbonyl-4-phenyl-4-[3,5-bis(trifluoromethyl) benzoyloxymethyl]piperidine

HRID 962468Notes

Reaction equation

HRID 962468 reaction equation
Cl.CN(C)CCCN=C=NCC.[F:13][C:14]([F:29])([F:28])[C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[C:18]([OH:20])=[O:19].[C:30]([O:34][C:35]([N:37]1[CH2:42][CH2:41][C:40]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([CH2:43]O)[CH2:39][CH2:38]1)=[O:36])([CH3:33])([CH3:32])[CH3:31]>CN(C)C1C=CN=CC=1.CN(C)C=O.O>[C:30]([O:34][C:35]([N:37]1[CH2:38][CH2:39][C:40]([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)([CH2:43][O:19][C:18](=[O:20])[C:17]2[CH:16]=[C:15]([C:14]([F:28])([F:29])[F:13])[CH:23]=[C:22]([C:24]([F:27])([F:25])[F:26])[CH:21]=2)[CH2:41][CH2:42]1)=[O:36])([CH3:31])([CH3:32])[CH3:33]

Participants

7

Reactant 3

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate

Product 1

HCID 544361011-tert-Butoxycarbonyl-4-phenyl-4-[3,5-bis(trifluoromethyl) benzoyloxymethyl]piperidine

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (897 mg) was added to a stirred solution of 3,5-bis(trifluoromethyl) benzoic acid (292 mg) and 4-dimethylaminopyridine (483 mg) in dry dimethylformamide (20 ml). The resulting solution was stirred for 30 minutes then the compound of step (a) above (1.0 g) was added. The resulting solution was stirred at room temperature for 19 hours. At this time the reaction was diluted with water (200 ml) and extracted into ethyl acetate. The organic layers were separated, washed with water, brine, and dried over MgSO4. Filtration and removal of solvent under reduced pressure afforded a yellow oil. Purification by chromatography on silica gel (20% ethyl acetate/n-hexane) afforded the product as a clear oil. 1H NMR (360 MHz, CDCl3) δ 1.4 (9H, s), 1.95 (2H, m), 2.3 (2H, m), 3.03 (2H, m), 3.8 (2H, m), 4.35 (2H, s), 7.0-7.2 (5H, m), 8.01 (1H, s), 8.25 (2H, s).

Workup

  1. stirringThe resulting solution was stirred at room temperature for 19 hours
  2. extractionextracted into ethyl acetate
  3. customThe organic layers were separated
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationFiltration and removal of solvent under reduced pressure
  7. customafforded a yellow oil
  8. customPurification by chromatography on silica gel (20% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-c3e3eedbcfcf4c50b175458f1017b5e8
Source dataset
uspto-grants-1998_06
Patent number
US05760018

Reaction notes

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