Piperidin-4-ol → HCID 10302804, compound

HRID 1168319Notes

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

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. MS m/e (%): 552 (M+H+, 100), M.p. 150-152°C.

Workup

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

Sources & evidence

ORD record: ord-351cc7646b3647748ab989eb02928aa6
Source dataset: uspto-grants-2003_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06624176B2

Reaction notes

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