Dimethylformamide → (S)-3-chloro-N-(4-hydroxy-1-(4-(1-methyl-2-(2-methyl-1,3-dioxolan-2-yl)-1H-imidazol-4-yl)phenyl)butan-2-yl)-4-isopropoxybenzamide

HRID 1436202Notes

Reaction equation

HRID 1436202 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][C:33]=1[O:34][CH:35]([CH3:37])[CH3:36])[C:7]([NH:9][C@H:10]([CH2:28][CH2:29][OH:30])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:19]=[C:20]([C:24](=NO)[CH3:25])[N:21]([CH3:23])[CH:22]=2)=[CH:14][CH:13]=1)=[O:8].Br[CH2:39][CH2:40][O:41][Si](C(C)(C)C)(C)C.CN(C=[O:53])C>CCOC(C)=O>[Cl:3][C:4]1[CH:5]=[C:6]([CH:31]=[CH:32][C:33]=1[O:34][CH:35]([CH3:36])[CH3:37])[C:7]([NH:9][C@H:10]([CH2:28][CH2:29][OH:30])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[N:19]=[C:20]([C:24]3([CH3:25])[O:41][CH2:40][CH2:39][O:53]3)[N:21]([CH3:23])[CH:22]=2)=[CH:14][CH:13]=1)=[O:8]

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 24758Sodium hydrideHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 136388607(S)-3-chloro-N-(4-hydroxy-1-(4-(2-(1-(hydroxyimino)ethyl)-1-methyl-1H-imidazol-4-yl)phenyl)butan-2-yl)-4-isopropoxybenzamide

Product 1

HCID 57594713(S)-3-chloro-N-(4-hydroxy-1-(4-(1-methyl-2-(2-methyl-1,3-dioxolan-2-yl)-1H-imidazol-4-yl)phenyl)butan-2-yl)-4-isopropoxybenzamideYield 41%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of NaH (0.39 g, 9.3 mmol) in DMF (15 mL) was added a solution of 3 (1.9 g, 6.5 mmol) in DMF (10 mL) at 0° C. under nitrogen. The reaction was stirred for 1.5 hour, and then (2-bromoethoxy)-tert-butyldimethylsilane (2.09 mL, 9.7 mmol) was added. The reaction mixture was stirred overnight, diluted with EtOAc, quenched with aqueous ammonium chloride solution, and extracted with EtOAc (3×50 mL). The organic layers were combined and dried over Na2SO4. Purification with biotage (EtOAc) gave the product 4 (1.2 g, 41%) as light yellow solid.

Workup

  1. stirringThe reaction mixture was stirred overnight
  2. customquenched with aqueous ammonium chloride solution
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialdried over Na2SO4
  5. customPurification with biotage (EtOAc)

Sources & evidence

ORD record
ord-5b57eda5da5a41b89b54f01cc7fc7b54
Source dataset
uspto-grants-2009_11
Patent number
US07618981B2

Reaction notes

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