Reaction #7999

Reaction equation

(2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidine-carboxylic acid

DIEA

2-hydrazinopyridine

PyBrop

L-proline methyl ester

→

1-(3,3-Dimethyl-2-oxo-pentanoyl)-pyrrolidine-2-carboxylic acid N′-pyridine-2-yl-hydrazide

Solvents

THF

ethyl acetate

Water

Conditions

Workup

1. 1
   WashThe organic phase was washed with ammonium chloride solution
2. 2
   Dryingdried with MgSO4
3. 3
   OtherColumn chromatography (silica gel, ethyl acetate:methanol=10:0.5) gave a colorless oil

Procedure

A mixture of (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-pyrrolidine-carboxylic acid (482 mg, 2 mmol), prepared from L-proline methyl ester according to the procedure described in WO 96/40633, 2-hydrazinopyridine (364 mg, 2 mmol), PyBrop (932 mg, 2 mmol), DMAP (4-dimethyaminopyridine, 122 mg) and DIEA (4 mL) in THF (dry, 50 mL) was stirred at room temperature for 24 h. Water and ethyl acetate were added. The organic phase was washed with ammonium chloride solution, followed by brine, and dried with MgSO4. Column chromatography (silica gel, ethyl acetate:methanol=10:0.5) gave a colorless oil; 490 mg (74%); MS (m/z) 333 (M+1); 1H NMR (d6-DMSO) δ0.85 (t, J=8 Hz, 3 H), 1.21 (s, 3 H), 1.23 (s, 3 H), 1.7 (m, 2 H), 1.90 (m, 1 H), 2.10 (m, 2 H), 2.35 (m, 1 H), 3.49 (t, J=8 Hz, 2 H), 4.62 (m, 1 H), 6.76 (m, 2 H), 7.51 (t, J=6 Hz, 1 H), 8.14 (d, J=6 Hz, 1 H).

Source