Sodium hydride → HCID 69064230, compound

HRID 1821987Notes

Reaction equation

HRID 1821987 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[H-].[Na+].[Br:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=1F>CN(C=O)C>[Br:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[C:13]=1[O:8][CH:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 660484-Piperidinol, 1-methyl-HCID 27332601-Bromo-2,3-difluorobenzene

Product 1

HCID 69064230HCID 69064230, compoundYield 54.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
65 °C

Procedure

Add slowly a solution of 1-methyl-piperidin-4-ol (2.98 g) in DMF (20 mL) into a suspension of sodium hydride (95%) (0.72 g) in DMF (25 mL) at room temperature. Heat the mixture in an oil bath at 65° C. After 30 min., add 1-bromo-2,3-difluoro-benzene (5.0 g) and stir at 65° C. After 2 hr., partition the reaction mixture between water and ether, dry over anhydrous sodium sulfate, and evaporate to give a yellow oil. Separate on a silica gel column (110 g, solvent: ether, ether-2M NH3 in methanol 19:1, 9:1) to obtain 4-(2-bromo-6-fluoro-phenoxy)-1-methyl-piperidine (4.06 g, 54% yield) and the title compound (1.60 g, 21% yield). Mass spectrum (electric spray) m/z=288 (M+1), 290 (M+2+1); 1H NMR (CDCl3): 7.12 (m, 1H), 6.92 (m, 2H), 4.30 (m, 1H), 2.69 (m, 2H), 2.30 (s, 3H), 2.28 (m, 2H), 1.97 (m, 2H), 1.89 (m, 2H).

Workup

  1. waitAfter 2 hr
  2. custom, partition the reaction mixture between water and ether
  3. dry with materialdry over anhydrous sodium sulfate
  4. customevaporate
  5. customto give a yellow oil
  6. customSeparate on a silica gel column (110 g, solvent: ether, ether-2M NH3 in methanol 19:1, 9:1)

Sources & evidence

ORD record
ord-f870cacb644a47da9a46349ad0bac48f
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

Loading…