(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoicacid synthesis

6synthesis methods

Product Name:(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoicacid
CAS Number:1357575-28-0
Molecular formula:C25H24ClNO3
Molecular Weight:421.92

ethyl (R)-4-(4-((4'-chloro-[1,1'-biphenyl]-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate

1357575-11-1
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(R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoicacid

1357575-28-0
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Yield:1357575-28-0 79%

Reaction Conditions:

Stage #1: (R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoatewith water in tetrahydrofuran;methanol at 50;
Stage #2: with hydrogenchloride in water; pH=~ 5;

Steps:

40 (R)-4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoic acid

A solution of (R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11A (First Eluting Compound), 5.37 g, 11.93 mmol) in THF (160 ml), water (40 ml), and methanol (40 ml) was stirred at 50° C. overnight. The volatiles were removed under reduced pressure and the resulting residue was diluted with water (100 ml). The pH of the solution was adjusted to 5 with 1N aq. HCl (35 ml) promoting the formation of a precipitate. The white solid was collected via filtration and washed with water (150 ml). The filter cake was dried overnight under high vacuum at 50° C. to provide the title product (4.0 g, yield: 79%).¹H NMR (400 MHz, DMSO-d₆) δ ppm 0.63 (qd, 3.79 Hz, 1H) 0.72-1.00 (m, 2H) 1.35-1.49 (m, 1H) 1.67 (d, 1H) 2.28-2.39 (m, 1H) 2.46 (t, 1H) 3.43 (d, 1H) 3.59 (d, 1H) 4.09 (d, 1H) 6.63 (d, 2H) 6.91 (dd, 1H) 7.05-7.23 (m, 4H) 7.23-7.29 (m, 2H) 7.36 (d, 1H) 7.47 (d, 2H).LCMS: (ESI) m/z 422 [M+H]⁺.

References:

US2012/35134,2012,A1 Location in patent:Page/Page column 45; 46

1679-18-1 Synthesis