3-(Trifluoromethyl)phenylboronic acid → (3,5-Dimethyl-3'-trifluoromethyl-biphenyl-4-yl)-(4-hydroxy-[1,4']bipiperidinyl-1'-yl)-methanone

HRID 1692413Notes

Reaction equation

HRID 1692413 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]([N:11]2[CH2:16][CH2:15][CH:14]([N:17]3[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]3)[CH2:13][CH2:12]2)=[O:10])=[C:4]([CH3:24])[CH:3]=1.[F:25][C:26]([F:37])([F:36])[C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1>>[CH3:24][C:4]1[CH:3]=[C:2]([C:31]2[CH:30]=[CH:29][CH:28]=[C:27]([C:26]([F:37])([F:36])[F:25])[CH:32]=2)[CH:7]=[C:6]([CH3:8])[C:5]=1[C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]2)[CH2:13][CH2:12]1)=[O:10]

Participants

3

Reactant 2

HCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 66901547(4-Bromo-2,6-dimethyl-phenyl)-(4-hydroxy-[1,4']bipiperidinyl-1'-yl)-methanone

Product 1

HCID 25190068(3,5-Dimethyl-3'-trifluoromethyl-biphenyl-4-yl)-(4-hydroxy-[1,4']bipiperidinyl-1'-yl)-methanone

Procedure

In analogy to the procedures described for intermediates 3B, 3C, 1, 4B and for example 1, the title compound has been prepared by the following reaction sequence: i) 4-hydroxy-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester [Lawrence, L.; Rigby, A.; Sanganee, H.; Springthorpe, B. PCT Int. Appl. (2001), WO 2001077101 A1] was reacted with benzoyl chloride to give 4-benzoyloxy-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester; ii) 4-benzoyloxy-[1,4′]bipiperidinyl-1′-carboxylic acid tert-butyl ester was reacted with trifluoroacetic acid to give benzoic acid [1,4′]bipiperidinyl-4-yl ester; iii) 4-bromo-2,6-dimethyl-benzoic acid was converted into its acid chloride and reacted with benzoic acid [1,4′]bipiperidinyl-4-yl ester to give benzoic acid 1′-(4-bromo-2,6-dimethyl-benzoyl)-[1,4′]bipiperidinyl-4-yl ester; iv) benzoic acid 1′-(4-bromo-2,6-dimethyl-benzoyl)-[1,4′]bipiperidinyl-4-yl ester was saponified to give (4-bromo-2,6-dimethyl-phenyl)-(4-hydroxy-[1,4′]bipiperidinyl-1′-yl)-methanone; v) Suzuki reaction of (4-bromo-2,6-dimethyl-phenyl)-(4-hydroxy-[1,4′]bipiperidinyl-1′-yl)-methanone with 3-trifluoromethyl-phenyl boronic acid gave the title compound as light brown solid. MS: 461.3 (MH+).

Sources & evidence

ORD record
ord-f44a216e5e2a44e58b6ea53362bdcb1a
Source dataset
uspto-grants-2012_04
Patent number
US08153805B2

Reaction notes

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