Triethylamine → (2S)-2-(Hydroxymethyl)pyrrolidine-1-carbaldehyde

HRID 467974Notes

Reaction equation

HRID 467974 reaction equation
FC(F)C1C([C:8](Cl)=[O:9])=CN(C)N=1.[NH:13]1[CH2:17][CH2:16][CH2:15][C@H:14]1[CH2:18][OH:19].C(N(CC)CC)C>ClCCl>[OH:19][CH2:18][C@@H:14]1[CH2:15][CH2:16][CH2:17][N:13]1[CH:8]=[O:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 640091L-ProlinolHCID 153401103-(Difluoromethyl)-1-methyl-1 H-pyrazole-4-carbonyl chloride

Product 1

HCID 12349566(2S)-2-(Hydroxymethyl)pyrrolidine-1-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

At a temperature of 0° C., a solution of 3-difluoromethyl-1-methyl-1H-pyrazole-4-carbonyl chloride (1.9 g, 10.0 mol) in dichloromethane (40 ml) was added dropwise to a stirred solution of (S)-pyrrolidin-2-yl-methanol (1.0 g, 10.0 mmol) and triethylamine (2.8 ml, 20.0 mmol) in dichloromethane 60 ml. The reaction mixture was stirred for 10 minutes at ambient temperature and then allowed to stand for 3 h at ambient temperature. The reaction mixture was washed with 1M NaOH (30 ml) and 2M HCl (30 ml) and then dried over Na2SO4. After removal of the solvent, the residue (1.76 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:dichloromethane/methanol 9:1). 1.28 g (49% of theory) of (3-difluoromethyl-1-methyl-1H-pyrazol-4-yl)-((S)-(2-hydroxymethyl-pyrrolidin-1-yl)-methanone was obtained in form of an oil.

Workup

  1. waitto stand for 3 h at ambient temperature
  2. washThe reaction mixture was washed with 1M NaOH (30 ml) and 2M HCl (30 ml)
  3. dry with materialdried over Na2SO4
  4. customAfter removal of the solvent
  5. customthe residue (1.76 g in the form of an oil) was purified by flash chromatography over silica gel (eluent:dichloromethane/methanol 9:1)

Sources & evidence

ORD record
ord-86a3a9d8f01a47dab322786f42d9fbec
Source dataset
uspto-grants-2014_01
Patent number
US08623902B2

Reaction notes

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