Benzyl Bromide → (R)-tert-Butyl 1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropylcarbamate

HRID 1037481Notes

Reaction equation

HRID 1037481 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[N:13]=[C:12]([C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:15]([CH3:18])([CH3:17])[CH3:16])[NH:11][N:10]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:33](Br)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>CN(C=O)C>[CH2:33]([N:11]1[C:12]([C@H:14]([NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:15]([CH3:18])([CH3:17])[CH3:16])=[N:13][C:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])=[N:10]1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 10796Cesium carbonateHCID 59781125(R)-tert-butyl 1-(3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropylcarbamate

Product 1

HCID 59781123(R)-tert-Butyl 1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropylcarbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred suspension of (R)-tert-butyl 1-(3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropylcarbamate (5.89 g, 16.1 mmol) and Cs2CO3 (10.5 g, 32.2 mmol) in DMF (46 mL, 0.35 M) was added benzyl bromide (2.11 mL, 17.7 mmol). Once the organic layer was separated and washed with H2O, brine, then dried over Na2SO4, filtered, and evaporated in vacuo to give (R)-tert-butyl 1-(1-benzyl-3-(2,5-difluorophenyl)-1H-1,2,4-triazol-5-yl)-2,2-dimethylpropyl-carbamate. The desired regioisomer was obtained on silica gel column (0% to 100% EtOAc in Hexanes, 3.25 g, 44.3%). The structure was verified by 1H NMR nOe experiments.

Workup

  1. customOnce the organic layer was separated
  2. washwashed with H2O, brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-7ccb3a391ddd4768bffc9786a6edc212
Source dataset
uspto-grants-2013_10
Patent number
US08546434B2

Reaction notes

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