Hydrochloric Acid → HCID 9817140, compound

HRID 481995Notes

Reaction equation

HRID 481995 reaction equation
C([Li])(CC)C.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[N:19]12[CH2:26][CH2:25][CH:22]([CH2:23][CH2:24]1)[C:21](=[O:27])[CH2:20]2.Cl>C1CCCCC1.O1CCCC1>[C:10]1([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:12][C:7]([C:21]2([OH:27])[CH:22]3[CH2:25][CH2:26][N:19]([CH2:24][CH2:23]3)[CH2:20]2)=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 71014-BromobiphenylHCID 195073-QuinuclidinoneHCID 178418400CID 53628100

Product 1

HCID 9817140HCID 9817140, compoundYield 41.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8078CyclohexaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of sec-butyllithium in cyclohexane (100 ml, 1.3M) was added dropwise with stirring to a solution of 4-bromobiphenyl (25 g) in dry tetrahydrofuran (240 ml) under an argon atmosphere at -78° C. The mixture was stirred for 5 minutes and a solution of quinuclidin-3-one (12 g) in dry tetrahydrofuran (100 ml) added during 20 minutes. Stirring was continued at -78° C. for 30 minutes and the mixture allowed to reach room temperature over 2 hours. 2M Hydrochloric acid (225 ml) was added keeping the reaction temperature below 10° C. The aqueous layer was separated and washed with diethyl ether (2×300 ml) before the addition of excess sodium hydroxide solution (density 1.35 g/cm3) to pH14. The mixture was extracted with ethyl acetate which had been heated to 50° C. and the ethyl acetate phase separated, dried (Na2SO4) and evaporated to yield a colourless solid which crystallised from ethyl acetate to give 3-(biphenyl-4-yl)-3-hydroxyquinuclidine (11.0 g) m.p. 165°-166° C.; microanalysis, found: C, 81.1; H, 7.5; N, 5.2%; C19H21NO 0.1H2O requires: C, 81.1; H, 7.5; N, 5.0%; NMR (CDCl3 /CD3CO2D): 1.7-1.9(3H, m,), 2.5(1H, m), 2.5-2.7(1H, m), 3.2-3.5(4H, m), 3.7(1H, dd), 4.0(1H, dd) and 7.3-7.7(9H, m); m/z 279 (M+).

Workup

  1. stirringStirring
  2. waitwas continued at -78° C. for 30 minutes
  3. waitto reach room temperature over 2 hours
  4. customthe reaction temperature below 10° C
  5. customThe aqueous layer was separated
  6. washwashed with diethyl ether (2×300 ml) before the addition of excess sodium hydroxide solution (density 1.35 g/cm3) to pH14
  7. extractionThe mixture was extracted with ethyl acetate which
  8. customthe ethyl acetate phase separated
  9. dry with materialdried (Na2SO4)
  10. customevaporated
  11. customto yield a colourless solid which
  12. customcrystallised from ethyl acetate

Sources & evidence

ORD record
ord-5d4d976024f048d5933294c8240db91f
Source dataset
uspto-grants-1998_08
Patent number
US05792777

Reaction notes

Loading…