Triethylamine → HCID 86680515, compound

HRID 1184596Notes

Reaction equation

HRID 1184596 reaction equation
Cl.[OH:2][C@H:3]1[CH2:7][NH:6][C@H:5]([C:8]([O:10][CH3:11])=[O:9])[CH2:4]1.[CH2:12]([N:14](CC)CC)[CH3:13].BrCC#N>CO>[C:12]([CH2:13][N:6]1[CH2:7][C@H:3]([OH:2])[CH2:4][C@H:5]1[C:8]([O:10][CH3:11])=[O:9])#[N:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 11534BromoacetonitrileHCID 114353194-Hydroxy-L-proline methyl ester hydrochloride

Product 1

HCID 86680515HCID 86680515, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of (2S,4R)-methyl 4-hydroxypyrrolidine-2-carboxylate hydrochloride (1 g, 5.51 mmol; Chem Impex) and triethylamine (1.919 mL, 13.77 mmol) in methanol (2 mL) was added 2-bromoacetonitrile (0.391 mL, 5.78 mmol) dropwise. The reaction was stirred at room temperature for 1 hour and then concentrated in vacuo. The residue was partitioned between water (10 mL) and dichloromethane (10 mL), and the organic layer was separated and concentrated. The resulting crude oil was purified by flash chromatography using an Agilent Technologies SuperFlash SF15-12 g cartridge eluting with a gradient of 10-100% ethyl acetate/hexanes over 15 minutes to isolate (2S,4R)-methyl 1-(cyanomethyl)-4-hydroxypyrrolidine-2-carboxylate (375 mg, 2.036 mmol, 37.0% yield) as an oil that solidified on standing. 1H NMR (300 MHz, CDCl3) δ ppm 4.50 (m, 1H), 3.92 (d, J=17.6 Hz, 1H), 3.76 (s, 3H), 3.73 (d, J=17.6 Hz, 1H), 3.71 (t, J=10.3 Hz, 1H), 3.47 (dd, J=10.0, 5.6 Hz, 1H), 2.72 (dd, J=10.0, 4.1 Hz, 1H), 2.23 (dddd, J=13.5, 10.0, 8.2, 5.5 Hz, 2H), 1.67 (d, J=4.6 Hz, 1H); MS (ESI+) m/z 185 (M+H)+.

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue was partitioned between water (10 mL) and dichloromethane (10 mL)
  3. customthe organic layer was separated
  4. concentrationconcentrated
  5. customThe resulting crude oil was purified by flash chromatography
  6. washeluting with a gradient of 10-100% ethyl acetate/hexanes over 15 minutes

Sources & evidence

ORD record
ord-8c9aa6fb3012443d84d0c0c21c001e77
Source dataset
uspto-grants-2014_03
Patent number
US08669255B2

Reaction notes

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