Sodium Bicarbonate → benzyl (3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3'-bipyrrolidine-1'-carboxylate

HRID 562576Notes

Reaction equation

HRID 562576 reaction equation
[O:1]=[C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][NH:20][CH2:19]1)[CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.O=[C:24]1[CH2:28][CH2:27][N:26]([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[O:30])[CH2:25]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.ClCCl>[F:13][C:12]([F:14])([F:15])[C:8]1[CH:7]=[C:6]([CH:11]=[CH:10][CH:9]=1)[C:5]([NH:4][CH2:3][C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20]([CH:28]2[CH2:24][CH2:25][N:26]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)=[O:30])[CH2:27]2)[CH2:19]1)=[O:1])=[O:16]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5612031-N-Cbz-3-pyrrolidinoneHCID 5049666Sodium triacetoxyborohydrideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 16061463benzyl (3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3'-bipyrrolidine-1'-carboxylateYield 109.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (500 mg, 1.59 mmol; prepared according to WO2004/050024A2) in methanol (5 mL) at room temperature was added benzyl 3-oxopyrrolidine-1-carboxylate (434 mg, 1.98 mmol) followed by sodium triacetoxyborohydride (470 mg, 2.22 mmol); the reaction mixture was stirred for 16 hours. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford, as a mixture of diastereomers, benzyl (3R)-3-[({[3-(trifluoromethyl)benzoyl]amino}acetyl)amino]-1,3′-bipyrrolidine-1′-carboxylate (906 mg, 88%) as a white solid. 1H-NMR (CDCl3) δ: 1.30-1.44 (m, 2H), 1.50-1.68 (m, 2H), 1.80-2.00 (m, 2H), 2.10-3.29 (m, 1H), 2.30-2.43 (m, 1H), 2.55-23.05 (m, 3H), 3.15-3.28 (m, 1H), 3.58-4.20 (m, 3H), 4.30-4.50 (m, 1H), 5.09 (s, 2H), 6.70-6.87 (m, 1H), 7.20-7.50 (m, 6H), 7.52 (t, J=8.7 Hz, 1H), 7.72 (d, J=7.2 Hz, 1H), 7.99 (d, J=7.2 Hz, 1H), 8.09 (s, 1H). MS m/z: 519 (M+1)

Workup

  1. customThe organic layer was separated
  2. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c082fb88a9f846b09ea211362c89fb28
Source dataset
uspto-grants-2011_11
Patent number
US08067415B2

Reaction notes

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