Tetrahydrofuran → tert-Butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-hydroxypiperidine-1-carboxylate

HRID 2075091Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2075091
Br[C:2]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:3]=1[CH2:4][O:5][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].C([Li])CCC.[C:26]([N:33]1[CH2:38][CH2:37][CH2:36][CH2:35][C:34]1=O)([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27].[O:40]1CCCC1>>[Si:6]([O:5][CH2:4][C:3]1[CH:13]=[C:14]([C:17]([F:20])([F:19])[F:18])[CH:15]=[CH:16][C:2]=1[C:36]1([OH:40])[CH2:37][CH2:38][N:33]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:34][CH2:35]1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]

Komponenten

5

Edukt 4

HCID 8028Tetrahydrofuran2×HCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylateHCID 58968745(2-Bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilaneHCID 178418339Butyllithium

Produkt 1

HCID 58968670tert-Butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-hydroxypiperidine-1-carboxylateAusbeute 43,9 %

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of (2-bromo-5-(trifluoromethyl)benzyloxy)(tert-butyl)dimethylsilane (904 mg; 2.45 mmol) in tetrahydrofuran (6.0 mL) at −78° C. was added dropwise n-butyllithium (1.5 mL; 3.75 mmol: 2.5M in hexanes). The reaction was stirred at −78° C. for 5 minutes. Then a solution of Boc-piperidone (831 mg; 4.17 mmol) in tetrahydrofuran (3 mL) was added dropwise into reaction. During addition reaction turned yellow in color. The reaction was stirred at −78° C. allowing it to warm to −40° C. within 1 hour. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous ammonium chloride, water and brine. The organic layer was dried sodium sulfate and concentrated under reduced pressure. The residue was purified over 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-15% ethyl acetate in heptane) to give 526 mg (43.9% yield) of a white solid. MS (ES+): Calc. 489.6, Found: 534.6 (M−HCO3). 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (dd, J=8.30, 8.71 Hz, 1H), 7.49 (d, J=1.66 Hz, 1H), 7.40 (d, J=8.30 Hz, 1H), 5.02 (s, 2H), 4.78 (s, 1H), 4.04 (d, J=16.18 Hz, 2H), 3.28 (dt, J=12.86, 2.90, 13.28, 2H), 2.00 (dt, J=12.86, 13.28, 4.98, 4.56, 2H), 1.84 (d, J=12.45 Hz, 2H), 1.50 (s, 9H), 0.92 (s, 9H), 0.13 (s, 6H).

Aufarbeitung

  1. additionDuring addition reaction
  2. stirringThe reaction was stirred at −78° C.
  3. temperatureto warm to −40° C. within 1 hour
  4. customThe reaction was quenched with water
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous ammonium chloride, water and brine
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified over 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-15% ethyl acetate in heptane)

Quellen und Nachweise

ORD-Eintrag
ord-c917ab0780ef49eba460197533c3dbbd
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07919506B2

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