반응 #1138

ord-9501c188203f4630b6447cbfdf010c16

반응 방정식

CC(C)(C)OC(=O)N1CCCC1c1cncc(Br)c1
5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine
c1ccc(P(c2ccccc2)c2ccccc2)cc1
triphenylphosphine
O=C([O-])[O-].[K+].[K+]
potassium carbonate
C#CC(C)(C)O
2-methyl-3-butyn-2-ol
C#CC(C)(O)Cc1cncc(C2CCCN2C(=O)OC(C)(C)C)c1
5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine
수율 76.4%

반응 조건

온도
25°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도the reaction flask was heated at 80° C. for 18 h
  2. 2
    여과this was filtered through celite
  3. 3
    기타The organic phase was separated
  4. 4
    추출the aqueous layer extracted with ethyl acetate (3×20 mL)
  5. 5
    세척the combined ethyl acetate extracts were washed with brine (20 mL)
  6. 6
    건조dried (MgSO4)
  7. 7
    농축concentrated in vacuo
  8. 8
    기타The crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants

실험 절차

A mixture of 5-bromo-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine (1 g, 3.06 mmol), 10% palladium on charcoal (80 mg, 0.077 mmol), copper(I)iodide (58 mg, 0.30 mmol), triphenylphosphine (80 mg, 0.30 mmol) and potassium carbonate (1.06 g, 7.65 mmol) in DME (5 mL) and water (5 mL) was stirred at 25° C. After 0.75 h 2-methyl-3-butyn-2-ol (0.74 mL, 7.65 mmol) was added and the reaction flask was heated at 80° C. for 18 h. Water (30 mL) and ethyl acetate (30 mL) were added to the cooled mixture and this was filtered through celite. The organic phase was separated and the aqueous layer extracted with ethyl acetate (3×20 mL) and the combined ethyl acetate extracts were washed with brine (20 mL), dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants to afford 5-(2-hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine as an oil (772 mg, 76%). LRMS (EI) m/e 231 (M+ +H --CO2 and isobutylene), 230 (M+ --CO2 and isobutylene), 229 (M+ --CO2 tBu); 1H NMR (CDCl3, 300 MHz): δ 8.56 (b-s, 1H), 8.37 (b-d, J=1.5 Hz, 1H), 7.53 (m, 1H), 4.93 (b-m, 0.5H), 4.76 (b-m, 0.5H), 3.5-3.7 (b-m, 2H), 2.36 (m, 1H), 1.75-2.0 (b-m, 3H), 1.72 (b-s, 1H), 1.63 (s, 6H), 1.45 (b-s, 3H), 1.21 (b-s, 6H).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US05723477uspto-grants-1998_03