Hydrochloric Acid → (S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylate

HRID 1684867Notes

Reaction equation

HRID 1684867 reaction equation
C(N(CC)C(C)C)(C)C.[C:10]([N:17]1[CH2:24][CH2:23][CH2:22][C@H:18]1[C:19]([OH:21])=O)([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:50][CH2:51][C:52]([C:54]1[CH:59]=[CH:58][C:57]([Br:60])=[CH:56][CH:55]=1)=[O:53]>CN(C=O)C>[Br:60][C:57]1[CH:56]=[CH:55][C:54]([C:52](=[O:53])[CH2:51][NH:50][C:19]([C@@H:18]2[CH2:22][CH2:23][CH2:24][N:17]2[C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])=[O:21])=[CH:59][CH:58]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 216392-Amino-1-(4-bromophenyl)ethanoneHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 56605334(S)-tert-butyl 2-((2-(4-bromophenyl)-2-oxoethyl)carbamoyl)pyrrolidine-1-carboxylateYield 95.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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]+.

Workup

  1. customDMF was removed in vacuo
  2. customthe resulting residue was partitioned between ethyl acetate (300 mL) and water (200 mL)
  3. washThe organic layer was washed with water (200 mL) and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customA silica gel mesh was prepared from the residue

Sources & evidence

ORD record
ord-a3d532fa498049e291e97daa38ae0927
Source dataset
uspto-grants-2012_04
Patent number
US08147818B2

Reaction notes

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