Lithium Hydroxide → Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylate

HRID 1612271Notes

Reaction equation

HRID 1612271 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]([CH2:45][CH3:46])[C:12]([NH:17][C@H:18]2[C@@H:22]([O:23]C(=O)C3C=CC([N+]([O-])=O)=CC=3)[CH2:21][N:20]([C:35]([O:37][CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[O:36])[CH2:19]2)=[N:13][C:14]=1[CH2:15][CH3:16].[Li+].[OH-].C(=O)(O)[O-].[Na+]>O1CCCC1.CO>[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]([CH2:45][CH3:46])[C:12]([NH:17][C@H:18]2[C@@H:22]([OH:23])[CH2:21][N:20]([C:35]([O:37][CH2:38][C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)=[O:36])[CH2:19]2)=[N:13][C:14]=1[CH2:15][CH3:16]

Participants

6

Reactant 3

HCID 3939Lithium HydroxideHCID 516892Sodium BicarbonateHCID 58583363Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-[(4-nitrobenzoyl)oxy]pyrrolidine-1-carboxylate

Product 1

HCID 58583263Benzyl(cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-hydroxypyrrolidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl (cis)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-[(4-nitrobenzoyl)oxy]pyrrolidine-1-carboxylate (3.17 g) in tetrahydofuran (38 ml) and methanol (3 ml) was added LiOH (1M(aq), 38 ml). The reaction mixture stirred 45 min and was poured into saturated sodium bicarbonate (100 ml). The aqueous layer was extracted ethyl acetate (2×200 ml), dried MgSO4, filtered and concentrated. MPLC chromatography on a biotage 40M column with 20-60% ethyl acetate/heptane provided the title compound as an oil (1.225 g, 50%): 1H NMR (400 MHz, CDCl3) δ) 7.50, 7.46-7.25, 5.18, 4.99, 4.89, 4.70, 4.51, 4.04, 3.75-3.59, 3.42-3.35, 2.70, 2.47, 2.19, 1.14; HRMS (FAB) calcd for C26H28Cl2N4O3+H 515.1616, found 515.1641. Anal. Calcd for C26H28Cl2N4O3: C, 60.59; H, 5.48; N, 10.87. Found: C, 60.32; H, 5.79; N, 10.54.

Workup

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

Sources & evidence

ORD record
ord-21eec652d99d4b93bbcae980357a1364
Source dataset
uspto-grants-2006_01
Patent number
US06992087B2

Reaction notes

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