1,2-Dichloroethane → tert-butyl (2R)-1-(4-bromophenyl)-4-(3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)-3-hydroxypiperidin-1-yl)-4-oxobutan-2-ylcarbamate

HRID 1096668Notes

Reaction equation

HRID 1096668 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][C:11]([OH:13])=O)=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.OC(C(F)(F)F)=O.[C:43]([C:47]1[N:51]([CH2:52][CH2:53][CH2:54][O:55][CH3:56])[C:50]([C:57]2([OH:63])[CH2:62][CH2:61][CH2:60][NH:59][CH2:58]2)=[N:49][CH:48]=1)([CH3:46])([CH3:45])[CH3:44]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C@@H:9]([NH:14][C:15](=[O:16])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:10][C:11]([N:59]2[CH2:60][CH2:61][CH2:62][C:57]([C:50]3[N:51]([CH2:52][CH2:53][CH2:54][O:55][CH3:56])[C:47]([C:43]([CH3:46])([CH3:44])[CH3:45])=[CH:48][N:49]=3)([OH:63])[CH2:58]2)=[O:13])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 7009737(3R)-4-(4-bromophenyl)-3-{[(tert-butoxy)carbonyl]amino}butanoic acidHCID 86761537HCID 86761537, compound

Product 1

HCID 68097983tert-butyl (2R)-1-(4-bromophenyl)-4-(3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)-3-hydroxypiperidin-1-yl)-4-oxobutan-2-ylcarbamateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R)-4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoic acid (45 mg, 81 gmol), EDC (24 mg, 125 μmol), HOBt (17 mg, 125 μmol) and 3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)piperidin-3-ol TFA salt (133C) (34 mg, 83 μmol) were added to a 10 mL round bottomed flask. DMF (420 μL) was added and the reaction was stirred overnight at room temperature. The solvent was removed and the residue was purified by preparatory LC/MS (35-50% CH3CN in H2O) to give the product tert-butyl (2R)-1-(4-bromophenyl)-4-(3-(5-tert-butyl-1-(3-methoxypropyl)-1H-imidazol-2-yl)-3-hydroxypiperidin-1-yl)-4-oxobutan-2-ylcarbamate (133D) (29 mg, 55% yield). ESI-MS:m/z 635.4 (M+H)+.

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by preparatory LC/MS (35-50% CH3CN in H2O)

Sources & evidence

ORD record
ord-a13651bdda764f768b278332085d719b
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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