Piperidin-4-ol → HCID 10302804, compound

HRID 1369142Notes

Reaction equation

HRID 1369142 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([CH3:24])[C:8](=[O:23])[C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12](Cl)=[N:11][CH:10]=1.[OH:34][CH:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1.C(N(C(C)C)C(C)C)C>CN(C1C=CN=CC=1)C.ClCCl.O>[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([CH:25]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:27]=1)[CH2:6][N:7]([CH3:24])[C:8]([C:9]1[C:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH3:21])=[CH:13][C:12]([N:38]2[CH2:39][CH2:40][CH:35]([OH:34])[CH2:36][CH2:37]2)=[N:11][CH:10]=1)=[O:23]

Participants

7

Reactant 3

HCID 79341Piperidin-4-olHCID 81531DiisopropylethylamineHCID 10277890N-(3,5-bis-trifluoromethyl-benzyl)-6-chloro-N-methyl-4-o-tolyl-nicotinamide

Product 1

HCID 10302804HCID 10302804, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 10.0 g (20.5 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-6-chloro-N-methyl-4-o-tolyl-nicotinamide, 3.1 g (31 mmol) 4-hydroxypiperidine, 10.6 ml (62 mmol) N-ethyldiisopropylamine and 0.13 g (1.0 mmol) 4-(N,N-dimethylamino)-pyridine was stirred at 140° C. for 70 h. After cooling to room temperature the residue was dissolved in a mixture of dichloromethane and water. The layers were separated and the aqueous layer was extracted with four portions of dichloromethane. The combined organic extracts were dried with sodium sulfate and concentrated to give 11.1 g of crude product. Flash chromatography afforded 9.0 g (80%) of the title compound as a white solid.

Workup

  1. temperatureAfter cooling to room temperature the residue
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with four portions of dichloromethane
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. concentrationconcentrated
  6. customto give 11.1 g of crude product

Sources & evidence

ORD record
ord-120528db7e994abbbf1eea97b590c70a
Source dataset
uspto-grants-2003_06
Patent number
US06576762B2

Reaction notes

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