3-Quinuclidinol, (-)- → 2-Cyclohexyl-2-hydroxy-2-thien-2-ylacetic acid (3r)-1-azabicyclo[2.2.2]oct-3-yl ester

HRID 1244457Notes

Reaction equation

HRID 1244457 reaction equation
[CH3:1][O:2][C:3](=[O:17])[C:4]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([OH:10])[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1.O[C@@H:19]1[CH:24]2C[CH2:26][N:21]([CH2:22][CH2:23]2)[CH2:20]1>C1(C)C=CC=CC=1>[N:21]12[CH2:22][CH2:23][CH:24]([CH2:19][CH2:20]1)[C@@H:1]([O:2][C:3](=[O:17])[C:4]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)([OH:10])[C:5]1[S:6][CH:7]=[CH:8][CH:9]=1)[CH2:26]2

Participants

4

Reactant 2

HCID 914043-Quinuclidinol, (-)-HCID 669594652-Cyclohexyl-2-hydroxy-2-thien-2-ylacetic Acid Methyl Ester

Product 1

HCID 669591842-Cyclohexyl-2-hydroxy-2-thien-2-ylacetic acid (3r)-1-azabicyclo[2.2.2]oct-3-yl esterYield 40.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Prepared using the same method as for Intermediate I-1, but from 16.2 g (0.064 mol) of 2-Cyclohexyl-2-hydroxy-2-thien-2-ylacetic acid methyl ester (Intermediate I-12), dissolved in 400 ml of toluene, 9.5 g (0.074 mol) of (3R)-3-hydroxy-1-azabicyclo[2.2.2]octane and 1.51 g (0.038 mol) of HNa (60% dispersion In mineral oil). The oil obtained (10.97 g) was purified by chromatography on silica gel, eluting with chloroform/methanol/ammonia 95:5:0.5, to obtain 8.97 g of a pure product as a mixture of diastereomers, structure confirmed by 1H-RMN. Three crystallisations of this mixture from ethyl ether yield 1.68 g (15.2%) of a pure diastereomer (Intermediate I-6a). The mother liquors of the crystallisations were enriched with the other diastereomer (Intermediate I-6b).

Workup

  1. customPrepared
  2. customThe oil obtained (10.97 g)
  3. customwas purified by chromatography on silica gel
  4. washeluting with chloroform/methanol/ammonia 95:5:0.5

Sources & evidence

ORD record
ord-ce1c395e49c94fee9380b09ccf4ec2ae
Source dataset
uspto-grants-2006_10
Patent number
US07122558B2

Reaction notes

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