Sodium hydride → HCID 59774633, compound

HRID 340096Notes

Reaction equation

HRID 340096 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:22])[CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH2:10]2)=[CH:4][CH:3]=1.[H-].[Na+].Cl.Cl[CH2:27][CH2:28][N:29]([CH3:31])[CH3:30]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([O:22][CH2:27][CH2:28][N:29]([CH3:31])[CH3:30])[CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:13][CH2:14]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11461534HCID 11461534, compoundHCID 11636816N,N-Dimethylaminoethyl chloride hydrochloride

Product 1

HCID 59774633HCID 59774633, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 4-((4-chlorophenyl)(hydroxyl)methyl)piperidine-1-carboxylate (1.25 g, 3.84 mmol) in DMF (50 mL) was added sodium hydride 60% w/w dispersion on mineral oil (384 mg, 9.59 mmol). The reaction mixture was stirred for 10 minutes at room temperature then 2-chloro-N,N-dimethylethanamine hydrochloride (608 mg, 4.22 mmol) ws added. The reaction mixture was stirred at 70° C. for 12 h. LC-MS of the reaction mixture showed no more starting material. The reaction mixture was cooled to room temperature and was diluted with EtOAc (50 mL) and washed with 10% LiCl in water (2×50 mL) followed by water (50 mL) and brine (50 mL). The organic layer was dried over Na2SO4, filtered and concentrated to yield tert-butyl 4-((4-chlorophenyl)(2-(dimethylamino)ethoxy)methyl)piperidine-1-carboxylate that was purified by reversed phase HPLC followed by separation on enantiomers by SFC. (253 mg and 246 mg, 33%) m/z: 397 (MH+)

Workup

  1. stirringThe reaction mixture was stirred at 70° C. for 12 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. washwashed with 10% LiCl in water (2×50 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8afad25c0e994342a0576c8f012295a1
Source dataset
uspto-grants-2014_11
Patent number
US08895566B2

Reaction notes

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