Methyl iodide → tert-Butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-methoxypiperidine-1-carboxylate

HRID 2075092Notes

Reaction equation

HRID 2075092 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:11]=1[C:20]1([OH:33])[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:37]>O1CCCC1>[Si:1]([O:8][CH2:9][C:10]1[CH:15]=[C:14]([C:16]([F:17])([F:18])[F:19])[CH:13]=[CH:12][C:11]=1[C:20]1([O:33][CH3:37])[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58968670tert-Butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 58968693tert-Butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-methoxypiperidine-1-carboxylateYield 100.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of tert-butyl 4-(2-((tert-butyldimethylsilyloxy)methyl)-4-(trifluoromethyl)phenyl)-4-hydroxypiperidine-1-carboxylate (526 mg; 1.07 mmol) in tetrahydrofuran (6 mL) at 0° C. was added sodium hydride (75 mg; 60% dispersion in mineral oil). The reaction was stirred for 10 minutes. Then iodomethane (0.10 mL; 1.61 mmol) was added. The reaction was stirred for 72 hours at room temperature. The reaction was quenched with water and 2N hydrochloric acid. The reaction was extracted with ethyl acetate. The organic layer was washed with water and brine. It was dried sodium sulfate and concentrated under reduced pressure. The residue was purified by 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-20% ethyl acetate in heptane) to give 540 mg (99.8% yield) of a colorless gum. MS (ES+): Calc: 503.6, Found: 445.4 (M−1BuH). 1H NMR (400 MHz, CDCl3) δ ppm 8.08 (s, 1H), 7.49, (dd, J=7.88, 8.30 Hz, 1H), 7.31 (d, J=8.30 Hz, 1H), 5.03 (s, 2H), 4.03 (bs, 2H), 3.16 (bs, 2H), 2.97 (s, 3H), 2.15 (d, J=12.86 Hz, 2H), 1.85 (bs, 2H), 1.48 (s, 9H), 0.98 (s, 9H), 0.14 (s, 6H).

Workup

  1. stirringThe reaction was stirred for 72 hours at room temperature
  2. customThe reaction was quenched with water and 2N hydrochloric acid
  3. extractionThe reaction was extracted with ethyl acetate
  4. washThe organic layer was washed with water and brine
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-f18d7c86691442549118ac49c1873432
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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