Sodium hydride → (Rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-[7-oxo-4-(3-trifluoromethyl-phenyl)-[1,4]diazepan-1-yl]-butyric acid methyl ester

HRID 1096214Notes

Reaction equation

HRID 1096214 reaction equation
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([N:9]2[CH2:15][CH2:14][C:13](=[O:16])[NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:7][CH:8]=1.[H-].[Na+].[CH3:21][O:22][C:23](=[O:36])[CH:24](I)[CH2:25][CH2:26][O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29].OP([O-])(O)=O.[K+]>CN(C=O)C>[CH3:21][O:22][C:23](=[O:36])[CH:24]([N:12]1[C:13](=[O:16])[CH2:14][CH2:15][N:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:1])([F:17])[F:18])[CH:4]=2)[CH2:10][CH2:11]1)[CH2:25][CH2:26][O:27][Si:28]([C:31]([CH3:33])([CH3:32])[CH3:34])([CH3:29])[CH3:30]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516951Monobasic potassium phosphateHCID 217545091-(3-Trifluoromethyl-phenyl)-[1,4]diazepan-5-oneHCID 87149689(Rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester2×

Product 1

HCID 66783316(Rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-[7-oxo-4-(3-trifluoromethyl-phenyl)-[1,4]diazepan-1-yl]-butyric acid methyl esterYield 217.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 1.60 g (1.94 mmol) of 1-(3-trifluoromethyl-phenyl)-[1,4]diazepan-5-one in 15 ml of DMF was treated at 0° C. with 0.33 g (7.44 mmol) of NaH (55% dispersion in oil). After 20 min at this temperature, the suspension was warmed to RT and added to a cooled solution (0° C.) of 2.33 g (6.50 mmol) of (rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester (intermediate 1) in 15 ml of DMF. The solution was stirred 6 h at 0° C. and neutralized with cold 10% aq. KH2PO4 solution and extracted with Et2O (3×). The organic phases were washed with 10% aq. KH2PO4 solution, dried over Na2SO4 evaporated and purified by flash silica gel column (CH2Cl2:Et2O 4:1 to 2:1) to yield 2.06 g (68%) of the title compound as light yellow oil. MS: 489.2 (MH+)

Workup

  1. extractionextracted with Et2O (3×)
  2. washThe organic phases were washed with 10% aq. KH2PO4 solution
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. custompurified by flash silica gel column (CH2Cl2:Et2O 4:1 to 2:1)

Sources & evidence

ORD record
ord-71910e5679614fa8921bc7053889490f
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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