Potassium Carbonate → N-methoxy-N-methyl-3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carboxamide

HRID 2040661Notes

Reaction equation

HRID 2040661 reaction equation
C([O-])([O-])=O.[K+].[K+].[CH3:7][Si:8]([CH2:11][CH2:12][O:13][CH2:14]Cl)([CH3:10])[CH3:9].[CH3:16][O:17][N:18]([CH3:39])[C:19]([CH:21]1[CH2:24][CH:23]([CH2:25][C:26]2[NH:30][C:29]3[CH:31]=[CH:32][C:33]([C:35]([F:38])([F:37])[F:36])=[CH:34][C:28]=3[N:27]=2)[CH2:22]1)=[O:20]>CN(C=O)C.O.[Cl-].[Na+].O>[CH3:16][O:17][N:18]([CH3:39])[C:19]([CH:21]1[CH2:22][CH:23]([CH2:25][C:26]2[N:30]([CH2:14][O:13][CH2:12][CH2:11][Si:8]([CH3:10])([CH3:9])[CH3:7])[C:29]3[CH:31]=[CH:32][C:33]([C:35]([F:38])([F:37])[F:36])=[CH:34][C:28]=3[N:27]=2)[CH2:24]1)=[O:20]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178502665HCID 178502665, compound

Product 1

HCID 86666119N-methoxy-N-methyl-3-{[5-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carboxamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

K2CO3 (381 mg, 2.76 mmol), followed by SEM-Cl (430 μl, 2.43 mmol) was added to a solution of the N-methoxy-N-methyl-3-{[5-(trifluoromethyl)-1H-1,3-benzodiazol-2-yl]methyl}cyclobutane-1-carboxamide (754 mg, 2.21 mmol) in DMF (10 ml) at RT and stirred overnight. The reaction was monitored by LCMS. The reaction mixture was diluted with water (3 ml), brine (30 ml) and then extracted with EtOAc (2×50 ml). This was dried over Na2SO4, filtered and evaporated to give a clear orange oil. Purification by silica gel column chromatography, eluting with EtOAc:heptanes (1:1-1) gave the desired products as a beige oils as a single regioisomer (217 mg, 21%); MS (ESI+) for C22H32F3N3O3Si m/z 472.55 [M+H]+; HPLC purity 99% (ret. time, 2.37 min); 1H NMR (250 MHz, CHLOROFORM-d) δH ppm −0.31-0.22 (9 H, m), 0.83-1.00 (2 H, m), 2.03-2.25 (2 H, m), 2.30-2.74 (2 H, m), 2.85-3.14 (3 H, m), 3.18 (3 H, s), 3.32-3.60 (3 H, m), 3.61-3.72 (3 H, m), 5.52 (2 H, s), 7.51 (1 H, dd, J=8.38, 1.22 Hz), 7.70 (1 H, s), 7.79 (1 H, d, J=8.53 Hz) and as a mixture of regioisomers (280 mg, 27%); C22H32F3N3O3Si m/z 472.55 [M+H]+; HPLC purity 72% & 21% (ret. time, 2.39 & 2.36 min); 1H NMR (250 MHz, CHLOROFORM-d) δ ppm −0.08-0.01 (9 H, m), 0.81-0.99 (2 H, m), 1.94-2.24 (2 H, m), 2.38-2.74 (2 H, m), 2.90-3.14 (3 H, m), 3.14-3.22 (3 H, m), 3.33-3.63 (3 H, m), 3.63-3.70 (3 H, m), 5.40-5.64 (2 H, m), 7.40-7.74 (2 H, m), 7.75-8.14 (1 H, m).

Workup

  1. extractionextracted with EtOAc (2×50 ml)
  2. dry with materialThis was dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customto give a clear orange oil
  6. customPurification by silica gel column chromatography
  7. washeluting with EtOAc:heptanes (1:1-1)

Sources & evidence

ORD record
ord-f402dd1fda984350be5d057b6a6bcfb4
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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