Dichloromethane → {5-Chloro-6-[(3R)-3-methylpiperazin-1-yl]pyridin-3-yl}methanol

HRID 730907Notes

Reaction equation

HRID 730907 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[C:19](C(F)(F)F)=[CH:18][C:17]([CH2:24][OH:25])=[CH:16][N:15]=2)[CH2:10][C@H:9]1[CH3:26])=O)(C)(C)C.FC(F)(F)C(O)=O.[Cl:34]CCl>C1(C)C=CC=CC=1>[Cl:34][C:19]1[CH:18]=[C:17]([CH2:24][OH:25])[CH:16]=[N:15][C:14]=1[N:11]1[CH2:12][CH2:13][NH:8][C@H:9]([CH3:26])[CH2:10]1

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 11703510(2R)-4-(5-Hydroxymethyl-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 11550484{5-Chloro-6-[(3R)-3-methylpiperazin-1-yl]pyridin-3-yl}methanol

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of 4-(5-hydroxymethyl-3-trifluoromethyl-pyridin-2-yl)-2-methyl-piperazine-1-carboxylic acid tert-butyl ester from step (f) above (3.75 g, 10 mmol) in dichloromethane (10 mL) was added trifluoroacetic acid (10 mL, Aldrich) dropwise at 0° C. over a period of 10 min. The mixture was stirred at room temperature for 16 h and diluted with toluene (20 mL). The solvents were removed in vacuo and the residue was dissolved in EtOAc (100 mL), washed with saturated aqueous solution of NaHCO3 (2×30 mL) and brine (20 mL), dried over Na2SO4, and filtered. The solvent was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 90:10:1 mixture of MeOH/CH2Cl2/ammonium hydroxide to give the title compound as a white solid. MS (ESI, pos. ion) m/e: 276 (M+1).

Workup

  1. customThe solvents were removed in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (100 mL)
  3. washwashed with saturated aqueous solution of NaHCO3 (2×30 mL) and brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customThe solvent was evaporated in vacuo
  7. customthe residue was purified by silica gel column chromatography
  8. washeluting with 90:10:1 mixture of MeOH/CH2Cl2/ammonium hydroxide

Sources & evidence

ORD record
ord-956fed4c05c744d29d585c6467e5d3f7
Source dataset
uspto-grants-2009_09
Patent number
US07582761B2

Reaction notes

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