N,N-Dimethylglycine hydrochloride → N-tert-Butoxycarbonyl-trans-4-(N,N-Dimethylglycylamino)-L-Proline Methyl Ester

Temperature

0 °C

Triethylamine (362 μL), 1-hydroxybenzotriazole (160 mg), and 1-(3-dimethylamino-propyl)-3-ethylcarbodiimide hydrochloride (249 mg) were added to a mixture of N-tert-butoxycarbonyl-trans-4-amino-L-proline methyl ester(Compound D101 (M), 264 mg) and N,N-dimethylglycine hydrochloride (181 mg) in dichloromethane (10 mL) at 0° C. After stirring at 0° C. for 30 min and at room temperature for 18 hr, the solvent was removed in vacuo. The residue was diluted with saturated sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform then chloroform:methanol=50:1 to 30:1, v/v) to afford the title compound (264 mg) as a pale yellow oil. The compound appears as a mixture of rotamers: 1H NMR (400 MHz, CDCl3) δ 1.42 and 1.46 (each s, total 9H), 2.28 (s, 6H), 2.13-2.40 (m, 2H), 2.94 (s, 2H), 3.22-3.43 (m, 1H), 3.74 (s, 3H), 3.75-3.88 (m, 1H), 4.28-4.48 (m, 1H), and 4.50-4.62 (m, 1H).

1. customthe solvent was removed in vacuo
2. additionThe residue was diluted with saturated sodium hydrogen carbonate
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. customevaporated in vacuo
7. customThe residue was purified by silica gel column chromatography (chloroform

ORD record

ord-b74c582791514b53a9adc958d47ad61a

Source dataset

uspto-grants-2002_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06399629B1