2-Methyl-3-butyn-2-ol → 5-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridine

HRID 1489405

Reaktionsgleichung

Reaktionsgleichung von HRID 1489405
Br[C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:5]=[N:6][CH:7]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].[CH3:45][C:46]([OH:50])([C:48]#[CH:49])[CH3:47]>[Pd].COCCOC.O.[Cu]I.C(OCC)(=O)C>[OH:50][C:46]([CH3:47])([C:48]#[CH:49])[CH2:45][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:5]=[N:6][CH:7]=1

Komponenten

10

Edukt 4

HCID 82582-Methyl-3-butyn-2-olHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 19694337Tert-butyl 2-(5-bromopyridin-3-yl)pyrrolidine-1-carboxylate

Produkt 1

HCID 196943235-(2-Hydroxy-2-methyl-3-butynyl)-3-(1-tert-butyloxycarbonyl-2-pyrrolidinyl)pyridineAusbeute 76,4 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 23938PalladiumKatalysatorHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittel2×HCID 80711,2-DimethoxyethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

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).

Aufarbeitung

  1. temperaturethe reaction flask was heated at 80° C. for 18 h
  2. filtrationthis was filtered through celite
  3. customThe organic phase was separated
  4. extractionthe aqueous layer extracted with ethyl acetate (3×20 mL)
  5. washthe combined ethyl acetate extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel column chromatography with ethyl acetate:hexane (1:3 to 1:1) as eluants

Quellen und Nachweise

ORD-Eintrag
ord-37c206e8dea848eab0f6532cf4d14769
Quelldatensatz
uspto-grants-1997_10
Patentnummer
US05677459

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