Imidazole → HCID 86603582, compound

HRID 2223770Notes

Reaction equation

HRID 2223770 reaction equation
OC1CN[C@H](C(O)=O)C1.[C:10]([C:12]1[CH:39]=[CH:38][C:15]([CH2:16][C:17]2([C:34]([O:36][CH3:37])=[O:35])[CH2:21][C@@H:20]([OH:22])[CH2:19][N:18]2[C:23](=[O:33])[CH2:24][C:25]2[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=2)=[CH:14][CH:13]=1)#[N:11].N1C=CN=C1.[Si:45](Cl)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]>CN(C=O)C.O>[Si:45]([O:22][C@H:20]1[CH2:19][N:18]([C:23](=[O:33])[CH2:24][C:25]2[CH:30]=[C:29]([Cl:31])[CH:28]=[C:27]([Cl:32])[CH:26]=2)[C:17]([CH2:16][C:15]2[CH:14]=[CH:13][C:12]([C:10]#[N:11])=[CH:39][CH:38]=2)([C:34]([O:36][CH3:37])=[O:35])[CH2:21]1)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 69248L-Proline, 4-hydroxy-, cis-HCID 86603583HCID 86603583, compound

Product 1

HCID 86603582HCID 86603582, compoundYield 90%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A 4-Hydroxy-L-proline derivative, methyl (4R)-2-(4-cyanobenzyl)-1-[(3,5-dichlorophenyl)acetyl]-4-hydroxypyrrolidine-2-carboxylate 21 (10 mmol) and imidazole (1.5 g, 22.5 mmol) were suspended in DMF (25 mL) and treated with tert-butyl(dimethyl)silyl chloride (1.6 g, 10.5 mmol). The reaction was stirred for 20 h, poured into water (100 mL) and extracted with diethyl ether (Et2O) (4×30 mL). The organic extracts were combined and washed with 1N HCl aq. (2×30 mL), water (1×50 mL), sat. aqueous NaHCO3 solution (1×30 mL) and sat. aq. NaCl solution (1×30 mL). The organic layer was dried (MgSO4) and solvent removed in vacuo to give methyl (4R)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-cyanobenzyl)-1-[(3,5-dichlorophenyl)acetyl]pyrrolidine-2-carboxylate (23) (˜5 g, 90%), which was used as such in subsequent reaction without further purification, LCMS, (m/z) 561 (M++H).

Workup

  1. extractionextracted with diethyl ether (Et2O) (4×30 mL)
  2. washwashed with 1N HCl aq. (2×30 mL), water (1×50 mL), sat. aqueous NaHCO3 solution (1×30 mL) and sat. aq. NaCl solution (1×30 mL)
  3. dry with materialThe organic layer was dried (MgSO4) and solvent
  4. customremoved in vacuo

Sources & evidence

ORD record
ord-48009f999d964a40b86f76dcda471dc0
Source dataset
uspto-grants-2008_05
Patent number
US07375237B2

Reaction notes

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