Water → (R)-tert-butyl 4-((5-(benzyloxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate

HRID 921144Notes

Reaction equation

HRID 921144 reaction equation
[OH:1][C@H:2]([CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1([CH3:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1.[H-].[Na+].[CH2:25](Br)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.O>CN(C=O)C>[CH2:25]([O:1][C@H:2]([CH3:22])[CH2:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1([CH3:21])[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 118307135(R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate

Product 1

HCID 118307119(R)-tert-butyl 4-((5-(benzyloxy)hexyl)oxy)-4-methylpiperidine-1-carboxylateYield 60.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-tert-butyl 4-((5-hydroxyhexyl)oxy)-4-methylpiperidine-1-carboxylate (4.5 g, 14.27 mmol) in DMF (50 mL) at 0° C. was added 60% NaH (0.685 g, 17.12 mmol) and the resulting mixture was stirred at room temp for 1 h. Benzyl bromide (2.55 mL, 21.40 mmol) was then added and the mixture was stirred for 16 h. Water (20 mL) was then added and the mixture was extracted with ether (100 mL), washed with brine (25 ml), dried (Na2SO4), filtered and concentrated. The residue was then purified by Biotage (0-20% EtOAc/hexane) to afford (R)-tert-butyl 4-((5-(benzyloxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate (3.5 g, 8.63 mmol, 60.5% yield) as light yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.38-7.35 (m, 4H), 7.31-7.25 (m, 1H), 4.60 (d, J=11.8 Hz, 1H), 4.48 (d, J=11.8 Hz, 1H), 3.86-3.62 (m, 3H), 3.58-3.50 (m, 1H), 3.31 (t, J=6.3 Hz, 2H), 3.14 (br. s., 2H), 1.74 (d, J=12.9 Hz, 2H), 1.59-1.51 (m, 3H), 1.47 (s, 9H), 1.46-1.37 (m, 4H), 1.22 (d, J=6.1 Hz, 3H), 1.17 (s, 3H). LCMS (M+H)=406.3.

Workup

  1. stirringthe mixture was stirred for 16 h
  2. extractionthe mixture was extracted with ether (100 mL)
  3. washwashed with brine (25 ml)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was then purified by Biotage (0-20% EtOAc/hexane)

Sources & evidence

ORD record
ord-885105e4e0d24424b8f1cf4a7b55d123
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

Loading…