Réaction #1772049

Équation de réaction

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

Rendement 95.9%

Solvants

DMF

Conditions de réaction

Traitement

1. 1
   AutreDMF was removed in vacuo
2. 2
   Autrethe resulting residue was partitioned between ethyl acetate (300 mL) and water (200 mL)
3. 3
   LavageThe organic layer was washed with water (200 mL) and brine
4. 4
   Séchagedried (MgSO4)
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   AutreA silica gel mesh was prepared from the residue

Mode opératoire

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]+.

Source