Potassium bisulfate → (rac)-4-(tert-Butyl-dimethyl-silanyloxy)-2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-butyric acid methyl ester

HRID 2095479Notes

Reaction equation

HRID 2095479 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].CC([O-])(C)C.[K+].[CH3:27][O:28][C:29](=[O:42])[CH:30](I)[CH2:31][CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].S([O-])(O)(=O)=O.[K+]>C1COCC1>[CH3:27][O:28][C:29](=[O:42])[CH:30]([N:16]1[C:17](=[O:20])[CH2:18][CH2:19][N:13]([C:11](=[O:12])/[CH:10]=[CH:9]/[C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:14][CH2:15]1)[CH2:31][CH2:32][O:33][Si:34]([C:37]([CH3:39])([CH3:38])[CH3:40])([CH3:35])[CH3:36]

Participants

6

Reactant 4

HCID 516920Potassium bisulfateHCID 23665647Potassium tert-butoxideHCID 620449211-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one2×HCID 87149689(Rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester2×

Product 1

HCID 67074257(rac)-4-(tert-Butyl-dimethyl-silanyloxy)-2-{4-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-butyric acid methyl esterYield 349.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 0.313 g (0.100 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 5A) in 10 ml of THF was treated at 0° C. with 0.135 g (0.120 mmol) of potassium tert-butylate. After 10 min, 0.394 g (0.110 mmol) of (rac)-4-(tert-butyl-dimethyl-silanyloxy)-2-iodo-butyric acid methyl ester (intermediate 1) was added. The reaction was stirred 1 h at 0° C., 15 h at RT and then neutralized with cold 10% aq. potassium hydrogensulfate solution and extracted with diethyl ether (3×). The organic phases were washed with sat. aq. sodium hydrogencarbonate solution, 10% aq. sodium chloride solution, dried over Na2SO4 evaporated and purified by flash silica gel column (n-heptane/ethyl acetate 1:1 to 2:3) to yield 0.19 g (35%) of the titled compound as light yellow viscous oil. MS: 543.3 (MH+, 2Cl).

Workup

  1. extractionextracted with diethyl ether (3×)
  2. washThe organic phases were washed with sat. aq. sodium hydrogencarbonate solution, 10% aq. sodium chloride solution
  3. dry with materialdried over Na2SO4
  4. customevaporated
  5. custompurified by flash silica gel column (n-heptane/ethyl acetate 1:1 to 2:3)

Sources & evidence

ORD record
ord-bcd6b91900f246e9a8970e92864fa29f
Source dataset
uspto-grants-2013_05
Patent number
US08445674B2

Reaction notes

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