Oxygen → (3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acid

HRID 2191100Notes

Reaction equation

HRID 2191100 reaction equation
O=O.[CH2:3]([N:10]1[CH2:15][C:14]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)=[C:13]([C:23]([OH:25])=[O:24])[CH2:12][CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.[H][H]>[OH-].[Na+].CC(OC)(C)C.CO>[CH2:3]([N:10]1[CH2:11][CH2:12][CH:13]([C:23]([OH:25])=[O:24])[CH:14]([C:16]2[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=2)[CH2:15]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

8

Reactant 4

HCID 977OxygenHCID 8471TriethylamineHCID 594381771-Benzyl-5-(4-chloro-phenyl)-1,2,3,6-tetrahydro-pyridine-4-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 68479302(3RS,4SR)-1-benzyl-3-(4-chloro-phenyl)-piperidine-4-carboxylic acidYield 72.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 14798Sodium HydroxideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

A 185-mL stainless steel autoclave was charged under argon in a glove box (O2 content<2 ppm) with the hydrochloride salt of 1-benzyl-5-(4-chloro-phenyl)-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid (7.00 g, 21.36 mmol), [Ru(OAc)2((R)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(di-2-furylphosphine)] (81.30 mg, 0.11 mol), [Ru(OAc)2((S)-(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(di-2-furylphosphine)] (81.30 mg, 0.11 mol), triethylamine (3.00 mL, 21.42 mmol) and methanol (120 mL). The hydrogenation was run for 20 h at 30° C. under 40 bar of hydrogen. After the pressure was released, the white suspension was evaporated to dryness to yield 9.58 g of the crude title compound. The crude product was dissolved in 1 M NaOH (45 mL). TBME (50 mL) was added, the aqueous layer was separated and diluted with water (250 mL). Under stirring 2 M HCl (20.5 mL) was added (pH value=6.0). The formed precipitate was filtered off and washed with water (50 mL). The filter cake was dissolved in methanol (100 mL) and the colorless solution evaporated to dryness to yield 5.13 g (70%) of the title compound. MS (m/e): 330.2 [(M+H)+].

Workup

  1. customthe white suspension was evaporated to dryness
  2. customto yield 9.58 g of the crude title compound
  3. customthe aqueous layer was separated
  4. additiondiluted with water (250 mL)
  5. additionwas added (pH value=6.0)
  6. filtrationThe formed precipitate was filtered off
  7. washwashed with water (50 mL)
  8. dissolutionThe filter cake was dissolved in methanol (100 mL)
  9. customthe colorless solution evaporated to dryness

Sources & evidence

ORD record
ord-de3509487cbe4f5bb46e7324428ef0d3
Source dataset
uspto-grants-2012_12
Patent number
US08324248B2

Reaction notes

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