3-Quinuclidinone → 3-Quinuclidinol hydrochloride

HRID 1656688

Reaction equation

HRID 1656688 reaction equation
[N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=[O:9])[CH2:2]2.N[C@H](C(OC(C)(C)C)=O)CC1C=CC=CC=1.C([BH3-])#N.[Na+].[ClH:30].N1C=CC=CC=1>CO>[ClH:30].[OH:9][CH:3]1[CH:4]2[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]2)[CH2:2]1

Participants

6

Reactant 4

HCID 195073-QuinuclidinoneHCID 5003444Sodium cyanoborohydrideHCID 6931633tert-butyl (2S)-2-amino-3-phenylpropanoateHCID 10176127Pyridinium chloride

Product 1

HCID 27237253-Quinuclidinol hydrochlorideYield 74%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a solution of 9.00 g (56.25 mmol) 3-quinuclidinone and 4.15 g (18.75 mmol) Phe-O-t-Bu in 50 ml methanol was added over a 12 hour period a solution of 2.95 g (46.9 mmol) sodium cyanoborohydride in 13 ml methanol. After stirring for an additional 8 hours, 5.78 g (50.0 mmol) pyridine hydrochloride was added and after 11/2 hours stirring, sodium chloride was removed by filtration. The filtrate was concentrated to a foam which was treated with 15 ml methanol and 50 ml ethyl acetate to give a slurry of the byproduct 3-hydroxy quinuclidine hydrochloride (74% of excess) which was removed by filtration. The filtrate was concentrate to an oil and charged with 10 ml methanol to a 5×200 cm column of LH-20 and eluted with methanol. The product fraction contained 6.54 g of a mixture of diastereomers in a 55:45 ratio as established by HPLC.

Workup

  1. stirringafter 11/2 hours stirring
  2. customsodium chloride was removed by filtration
  3. concentrationThe filtrate was concentrated to a foam which
  4. additionwas treated with 15 ml methanol and 50 ml ethyl acetate

Sources & evidence

ORD record
ord-fb8f70ad73604df29cc5de5e117b6ef6
Source dataset
uspto-grants-1993_10
Patent number
US05254682

Linked notes

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