Diisopropylethylamine → HCID 69156077, compound

HRID 1793452Notes

Reaction equation

HRID 1793452 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:23](O)=[O:24])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:26][C:27]1[CH:33]=[CH:32][C:30]([NH2:31])=[CH:29][C:28]=1[O:34][CH3:35].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>ClCCl>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[CH2:11][CH2:10][C@H:9]1[C:23](=[O:24])[NH:31][C:30]1[CH:32]=[CH:33][C:27]([Cl:26])=[C:28]([O:34][CH3:35])[CH:29]=1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 131036924-Chloro-3-methoxyanilineHCID 69155886HCID 69155886, compound

Product 1

HCID 69156077HCID 69156077, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of (2S,5R)5-(3,4-dimethoxy-phenyl)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (2.50 g, 7.11 mmol, 1.0 equivalent), 4-chloro-3-methoxyaniline (1.12 g, 7.11 mmol, 1.0 equivalent), PyBrop coupling reagent (3.98 g, 8.54 mmol, 1.2 equivalents), and DIEA (1.86 ml, 10.7 mmol, 1.5 equivalents) in dichloromethane (35 ml) was allowed to stir at room temperature overnight. The reaction mixture was concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (100 ml) and washed with 1N NaOH (3×100 ml). The organic extract was dried over anhydrous Na2SO4 and concentrated in vacuo. The crude oil was filtered through a layer of silica and eluted with ethyl acetate:hexanes (1:1). The filtrate was concentrated in vacuo to afford (2S,5R)2-(4-chloro-3-methoxy-phenylcarbamoyl)-5-(3,4-dimethoxy-phenyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (3.48 g, 7.09 mmol, 100% yield). Analysis H1 NMR (400 MHz, CDCl3): 7.59 (1H, broad s), 7.23 (1H, m), 6.85–6.60 (4H, m) 4.64 (2H, m), 3.00 (3H, s), 3.83 (3H, s), 3.56 (3H, broad s), 2.62 (1H, broad m), 2.36 (1H, m), 2.11–1.89 (2H, m), 1.22 (9H, broad s). MS (LC-MS): Calculated for C25H31ClN2O6 490.19, found 491.15 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in ethyl acetate (100 ml)
  3. washwashed with 1N NaOH (3×100 ml)
  4. extractionThe organic extract
  5. dry with materialwas dried over anhydrous Na2SO4
  6. concentrationconcentrated in vacuo
  7. filtrationThe crude oil was filtered through a layer of silica
  8. washeluted with ethyl acetate:hexanes (1:1)
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-82d2100e72634c39bb308f04cdedd33c
Source dataset
uspto-grants-2006_07
Patent number
US07081458B2

Reaction notes

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