4-Nitrobenzoic Acid → Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-[(4-nitrobenzoyl)oxy]pyrrolidine-1-carboxylate

HRID 1824185Notes

Reaction equation

HRID 1824185 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:34][CH3:35])[C:12]([NH:17][C@H:18]2[C@H:22]([OH:23])[CH2:21][N:20]([C:24]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[O:25])[CH2:19]2)=[N:13][C:14]=1[CH2:15][CH3:16].[N+:36]([C:39]1[CH:47]=[CH:46][C:42]([C:43](O)=[O:44])=[CH:41][CH:40]=1)([O-:38])=[O:37].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.C(=O)(O)[O-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH2:34][CH3:35])[C:12]([NH:17][C@H:18]2[C@@H:22]([O:23][C:43](=[O:44])[C:42]3[CH:41]=[CH:40][C:39]([N+:36]([O-:38])=[O:37])=[CH:47][CH:46]=3)[CH2:21][N:20]([C:24]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)=[O:25])[CH2:19]2)=[N:13][C:14]=1[CH2:15][CH3:16]

Participants

7

Reactant 5

HCID 61084-Nitrobenzoic AcidHCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 516892Sodium BicarbonateHCID 58583410Benzyl(trans)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 58583363Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-[(4-nitrobenzoyl)oxy]pyrrolidine-1-carboxylateYield 84.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl(trans)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylate (2.93 g) in tetrahydrofuran (100 ml) was added p-nitrobenzoic acid (1.89 g), triphenyl phosphine (2.23 g) and di-tert-butyl azodicarboxylate (1.95 g). The reaction mixture was heated at 400C for 18 h and was poured into saturated sodium bicarbonate (200 ml). The aqueous layer was extracted with ethyl acetate (2×200 ml), dried MgSO4, filtered and concentrated. MPLC chromatography on a biotage 40 M column with 15–20% ethyl acetate/heptane provided the title compound as an oil (3.19 g, 84%): 1H NMR (400 MHz, CDCl3) δ) 8.35, 8.20, 7.49–7.22, 6.23, 5.81, 5.32, 5.20, 5.05, 4.83, 4.27, 3.95–3.85, 3.51, 2.58–2.41, 1.63, 1.32–1.14; (MS/CI) calcd for C33H31Cl2N5O3+H 664.5, found 664.1.

Workup

  1. extractionThe aqueous layer was extracted with ethyl acetate (2×200 ml), dried MgSO4
  2. filtrationfiltered
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-8b1a88fa6b1a46259155244bd3acce59
Source dataset
uspto-grants-2006_05
Patent number
US07041672B2

Reaction notes

Loading…