Sodium hydride → Tert-butyl 4-[(cyclopropylmethoxy)methyl]piperidine-1-carboxylate

HRID 341521Notes

Reaction equation

HRID 341521 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][OH:15])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].Br[CH2:19][CH:20]1[CH2:22][CH2:21]1>CN(C=O)C.CCOC(C)=O>[CH:20]1([CH2:19][O:15][CH2:14][CH:11]2[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]2)[CH2:22][CH2:21]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 66803103Tert-butyl 4-[(cyclopropylmethoxy)methyl]piperidine-1-carboxylateYield 98.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-boc-4-piperidinemethanol (0.500 g, 2.322 mmol) in DMF (10 mL) was added drop wise to a suspension of sodium hydride (60% in mineral oil) (0.186 g, 4.645 mmol) in dry DMF (15 mL) at 0 C. The mixture was stirred at 0 C for 15 minutes and room temperature for 10 minutes before being cooled down again and (bromomethyl)cyclopropane (0.227 mL, 2.322 mmol) was added drop wise. The reaction mixture was stirred at 0 C for 10 minutes, room temperature for 1 h and 80 C for 4 h. The reaction mixture was diluted with EtOAc (60 mL) and washed with water (3×20 mL). The aqueous washes were combined and re-extracted with EtOAc (3×20 mL). The organic extracts were combined, dried over sodium sulfate, filtered and evaporated to provide the title compound as a colorless oil (0.614 g, 98%). Method B HPLC-MS: MH+ requires m/z=270 Found: m/z=214 (MH+-tBu), Rt=2.33 min (83%).

Workup

  1. temperaturebefore being cooled down again
  2. stirringThe reaction mixture was stirred at 0 C for 10 minutes, room temperature for 1 h
  3. wait80 C for 4 h
  4. washwashed with water (3×20 mL)
  5. extractionre-extracted with EtOAc (3×20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-18472ed9d488464d86ddf5cf27da3c57
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

Loading…