تفاعل #1772049

معادلة التفاعل

N,N-Diisopropylethylamine

N-Boc-L-proline

HATU

HCl

2-amino-1-(4-bromo-phenyl)ethanone

→

(S)-tert-butyl 2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)pyrrolidine-1-carboxylate

المردود 95.9%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىDMF was removed in vacuo
2. 2
   أخرىthe resulting residue was partitioned between ethyl acetate (300 mL) and water (200 mL)
3. 3
   غسيلThe organic layer was washed with water (200 mL) and brine
4. 4
   تجفيفdried (MgSO4)
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated
7. 7
   أخرىA silica gel mesh was prepared from the residue

الإجراء التجريبي

N,N-Diisopropylethylamine (18 mL, 103.3 mmol) was added dropwise, over 15 minutes, to a heterogeneous mixture of N-Boc-L-proline (7.139 g, 33.17 mmol), HATU (13.324 g, 35.04 mmol), the HCl salt of 2-amino-1-(4-bromo-phenyl)ethanone (8.127 g, 32.44 mmol), in DMF (105 mL) and stirred at ambient condition for 55 minutes. DMF was removed in vacuo, and the resulting residue was partitioned between ethyl acetate (300 mL) and water (200 mL). The organic layer was washed with water (200 mL) and brine, dried (MgSO4), filtered, and concentrated. A silica gel mesh was prepared from the residue and submitted to flash chromatography (silica gel; 50-60% ethyl acetate/hexanes) to provide Example 14, (S)-tert-butyl 2-(2-(4-bromophenyl)-2-oxoethylcarbamoyl)pyrrolidine-1-carboxylate as a white solid (12.8 g). 1H NMR (DMSO-d6, δ=2.5 ppm, 400 MHz): δ 8.25-8.14 (m, 1H), 7.92 (br d, J=8.0, 2H), 7.75 (br d, J=8.6, 2H), 4.61 (dd, J=18.3, 5.7, 1H), 4.53 (dd, J=18.1, 5.6, 1H), 4.22-4.12 (m, 1H), 3.43-3.35 (m, 1H), 3.30-3.23 (m, 1H), 2.18-2.20 (m, 1H), 1.90-1.70 (m, 3H), 1.40/1.34 (two app br s, 9H). RT=1.70 min (condition 1); LCMS: Anal. Calcd. for C18H23BrN2NaO4: 433.07. found 433.09 [M+Na]+.

المصدر