HCID 59201260, compound → HCID 59201214, compound

HRID 1942297Notes

Reaction equation

HRID 1942297 reaction equation
C([O:8][CH2:9][C@H:10]([N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][C@H:17]1[C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[CH:28][CH:27]=1)[C:11]#[C:12][C:13]([CH3:15])=[CH2:14])C1C=CC=CC=1>CO.[Ni]>[OH:8][CH2:9][C@H:10]([N:16]1[CH2:21][CH2:20][C@@H:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][C@H:17]1[C:26]1[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:33])[F:34])=[CH:28][CH:27]=1)[CH2:11][CH2:12][CH:13]([CH3:14])[CH3:15]

Participants

4

Reactant 1

HCID 59201260HCID 59201260, compound

Product 1

HCID 59201214HCID 59201214, compound

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Procedure

A solution of methyl {(2S,4R)-1-{(1R)-1-[(benzyloxy)methyl]-4-methylpent-4-en-2-yn-1-yl}-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Example 28, 1.4 g, 2.80 mmol) in MeOH (15 ml) was hydrogenated over Raney nickel (˜1 g) at 50 psi on the Parr overnight at room temperature. MS showed mostly desired product, but still some alkene. Extra Raney nickel (˜1 g) was added and the hydrogenation was continued for a further 5 hours. MS showed the reduction to be almost complete. The catalyst was removed by filtration, washing with MeOH. The filtrate was evaporated. The residue was partitioned between DCM and water. The aqueous layer was extracted with DCM (×3). The combined extracts were dried (Na2SO4), filtered and evaporated to give the alkane (1.16 g) as an oil. This material was used without further purification. A solution of benzyl ether (above, 1.16 g, 2.294 mmol) in acetic acid (25 ml) was hydrogenated at 50 psi over 10% palladium on carbon (150 mg, 0.141 mmol) on the Parr at room temperature overnight. The catalyst was removed by filtration—washing with MeOH. The filtrate was evaporated—azeotroping with PhMe (×2). The residue was partitioned between DCM and saturated aqueous NaHCO3. The aqueous layer was extracted with DCM (×3). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (silica, 10-20-40% EtOAc/isohexanes) to give the alcohol. (795 mg) as an oil. This material was hydrolysed with NaOH in MeOH to give {(2S,4R)-1-[(1R)-1-(hydroxymethyl)-4-methylpentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid, M/Z 402 (MH+).

Sources & evidence

ORD record
ord-b115db2b44fc4bd7b11bc9b075d80136
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

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