Formic Acid → 2-(3-Pyridinylmethyl)-3-quinuclidinol

HRID 2246822Notes

Reaction equation

HRID 2246822 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH:8]2[C:13](=[O:14])[CH:12]3[CH2:15][CH2:16][N:9]2[CH2:10][CH2:11]3)[CH:2]=1.C(N(CC)CC)C.C(O)=O.C(=O)([O-])[O-].[K+].[K+].CCCCCC.CC(O)C.C(NCC)C>ClCCl.C(O)=O.C(N(CC)CC)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH:8]2[CH:13]([OH:14])[CH:12]3[CH2:11][CH2:10][N:9]2[CH2:16][CH2:15]3)[CH:2]=1

Participants

8

Reactant 5

HCID 284Formic AcidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 102200302-(Pyridin-3-ylmethyl)quinuclidin-3-oneHCID 21973129Hexane isopropanol diethylamine

Product 1

HCID 102200582-(3-Pyridinylmethyl)-3-quinuclidinolYield 49%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 11084032Triethylammonium formateSolvent

Conditions

Temperature
40 °C

Procedure

0.518 g (2.39 mmol) of racemic 2-(3-pyridinylmethyl)-3-quinuclidinone, 0.65 ml (4.66 mmol) of triethylamine, 0.44 ml (11.7 mmol) of formic acid (formic acid/triethylamine=5/2 to the substrate molar ratio), 5.5 mg (8.6×10−3 mmol, S/C=200) of RuCl [(S,S)— TsDPEN] (p-cymene) were introduced into a 20 mL Schlenk flask under an argon atmosphere and stirred for 19 hours at 40° C. The reaction liquid was diluted in dichloromethane, neutralized by potassium carbonate, and after removing the solids by filtration, the target substance was obtained with a yield of 49% by concentrating and drying to solids. By NMR spectroscopy it was confirmed that 2-(3-pyridinylmethyl)-3-quinuclidinol of only one of the diastereomers was obtained. The optical purity, determined by HPLC analysis (Daicel Chiralcel OD-H two columns connected in series, Hexane/2-propanol/diethylamine=80/20/0.1, 0.3 mL/min., 25° C., the retention times of the two types of optical isomers in the diastereomer obtained were 64.0 min. and 83.2 min.) was 85% ee.

Workup

  1. customThe reaction liquid
  2. customafter removing the solids
  3. filtrationby filtration
  4. customthe target substance was obtained with a yield of 49%
  5. concentrationby concentrating
  6. customdrying to solids
  7. customwas obtained
  8. customthe retention times of the two types of optical isomers in the diastereomer obtained
  9. waitwere 64.0 min. and 83.2 min.

Sources & evidence

ORD record
ord-6e93e21747524822babadab735d31aa2
Source dataset
uspto-grants-2010_03
Patent number
US07687630B2

Reaction notes

Loading…