Hydrochloric Acid → 3-(4'-Hydroxybiphenyl-4-yl)-3-hydroxy-quinuclidine hydrochloride

HRID 481998

반응식

HRID 481998 반응식
C([Li])(CC)C.Br[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][Si](C(C)(C)C)(C)C)=[CH:15][CH:14]=2)=[CH:9][CH:8]=1.[N:27]12[CH2:34][CH2:33][CH:30]([CH2:31][CH2:32]1)[C:29](=[O:35])[CH2:28]2.[ClH:36]>C1CCCCC1.O1CCCC1>[ClH:36].[OH:19][C:16]1[CH:15]=[CH:14][C:13]([C:10]2[CH:9]=[CH:8][C:7]([C:29]3([OH:35])[CH:30]4[CH2:33][CH2:34][N:27]([CH2:32][CH2:31]4)[CH2:28]3)=[CH:12][CH:11]=2)=[CH:18][CH:17]=1

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 195073-QuinuclidinoneHCID 3765121({4'-Bromo-[1,1'-biphenyl]-4-yl}oxy)(tert-butyl)dimethylsilaneHCID 178418400CID 53628100

생성물 1

HCID 190650473-(4'-Hydroxybiphenyl-4-yl)-3-hydroxy-quinuclidine hydrochloride

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8078Cyclohexane용매

실험 절차

A solution of sec-butyllithium in cyclohexane (7.4 ml, 1.3M) was added dropwise, with stirring, to a solution of 4-bromo-4'-(tert-butyldimethylsilyloxy)biphenyl (2.9 g) in dry tetrahydrofuran (30 ml) under an atmosphere of argon at -78° C. The mixture was stirred for 5 minutes and a solution of quinuclidin-3-one (0.9 g) in dry tetrahydrofuran (12 ml) was then added over a period of 2 minutes. The mixture was stirred at -78° C. for a further 30 minutes and the mixture then allowed to warm to room temperature over 2 hours. Aqueous 2M hydrochloric acid (18 ml) was added to the reaction mixture, whilst keeping the temperature of the reaction mixture below 10° C. The aqueous layer was separated and washed with diethyl ether (2×20 ml) before the addition of excess sodium hydroxide solution (density 1.35 g/cm3) to pH 14. The mixture was extracted with warm ethyl acetate (50° C.) and the ethyl acetate phase separated, dried (Na2SO4) and evaporated. The residue was dissolved in dry tetrahydrofuran (20 ml) and added to a solution of tetrabutyl ammonium fluoride in tetrahydrofuran (1.6 ml, 1.0M). The mixture was stirred at room temperature for 2 hours. The tetrahydrofuran was evaporated, an excess of saturated ethereal hydrogen chloride solution was added to precipitate a solid which was crystallised from methanol/ethyl acetate to give as a colourless solid, 3-(4'-hydroxybiphenyl-4-yl)-3-hydroxy-quinuclidine hydrochloride (0.93 g), m.p. 270°-271° C., microanalysis, found: C, 66.5; H, 6.5; N, 4.1%; C19H21NO2.HCl.0.66H2O requires: C, 66.5: H, 6.8: N, 4.1%; NMR ([CD3 ]2SO): 1.4-1.6(1H, m), 1.7-1.9(2H, m), 2.3-2.4(2H, m), 3.1-3.4(5H, m), 3.8-3.9(1H, d), 5.9(1H, s), 6.9-7.5(4H, d of d), 7.6(4H, s), 9.6(1H, s); m/Z 296 (M+H).

후처리

  1. stirringThe mixture was stirred at -78° C. for a further 30 minutes
  2. customthe temperature of the reaction mixture below 10° C
  3. customThe aqueous layer was separated
  4. washwashed with diethyl ether (2×20 ml) before the addition of excess sodium hydroxide solution (density 1.35 g/cm3) to pH 14
  5. extractionThe mixture was extracted with warm ethyl acetate (50° C.)
  6. customthe ethyl acetate phase separated
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. dissolutionThe residue was dissolved in dry tetrahydrofuran (20 ml)
  10. additionadded to a solution of tetrabutyl ammonium fluoride in tetrahydrofuran (1.6 ml, 1.0M)
  11. stirringThe mixture was stirred at room temperature for 2 hours
  12. customThe tetrahydrofuran was evaporated
  13. additionan excess of saturated ethereal hydrogen chloride solution was added
  14. customto precipitate a solid which
  15. customwas crystallised from methanol/ethyl acetate

출처 및 근거

ORD 기록
ord-1d5ac452d5414b35b9cd25f93c64cfd3
출처 데이터셋
uspto-grants-1998_08
특허 번호
US05792777

연결된 노트

불러오는 중…