Oxygen → (3R,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid

HRID 587343Notes

Reaction equation

HRID 587343 reaction equation
O=O.[CH2:3]([N:10]1[CH2:14][C:13]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)=[C:12]([C:22]([OH:24])=[O:23])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.COC1C(C2C(OC)=CC=CC=2P(C2OC=CC=2)C2OC=CC=2)=C(P(C2OC=CC=2)C2OC=CC=2)C=CC=1.[H][H]>CO>[CH2:3]([N:10]1[CH2:14][C@@H:13]([C:15]2[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=2)[C@@H:12]([C:22]([OH:24])=[O:23])[CH2:11]1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 977OxygenHCID 15307805(S)-(-)-2,2'-Bis(di-2-furanylphosphino)-6,6'-dimethoxy-1,1'-biphenylHCID 593718091-Benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acidHCID 178418361HCID 178418361, compound

Product 1

HCID 6558982(3R,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acidYield 97.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

An autoclave was charged under argon in a glove box (O2 content<2 ppm) with 1-benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid (1.00 g, 3.19 mmol), [Ru(OAc)2((S)-2-furyl-MeOBIPHEP)] (9.72 mg, 0.01 mmol) (2-furyl-MeOBIPHEP=(6,6′-dimethoxybiphenyl-2,2′-diyl)bis(di-2-furylphosphine) and methanol (30 ml). The asymmetric hydrogenation was run for 20 h at 30° C. under 40 bar of hydrogen (>95% conversion, determined by NMR). After the pressure was released, the grey suspension was evaporated to dryness to yield 1.01 g of the crude title compound. The crude product was dissolved in methanol (15 mL) and heated to reflux for 1 h. After cooling to ambient temperature it was stirred for 2 h at 0° C. The resulting suspension was filtered and dried (40° C., 15 mbar) for 2 h. affording the title compound (0.984 g, 95%, e.e. 99.8% R,R (chiral HPLC)) as white solid. MS m/e: 316.1 [M+H]+.

Workup

  1. customthe grey suspension was evaporated to dryness
  2. customto yield 1.01 g of the crude title compound
  3. temperatureheated
  4. temperatureto reflux for 1 h
  5. filtrationThe resulting suspension was filtered
  6. customdried (40° C., 15 mbar) for 2 h.

Sources & evidence

ORD record
ord-b73635d3a725417a9308812c794e29d4
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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