Azidotrimethylsilane → HCID 23582027, compound

HRID 238793Notes

Reaction equation

HRID 238793 reaction equation
[C:1]([CH2:3][C:4]([NH:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([C:36]([F:39])([F:38])[F:37])[CH:30]=1)([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:15])([F:14])[F:13])[CH:6]=1)#[N:2].[Si]([N:45]=[N+:46]=[N-:47])(C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C(Cl)Cl>[C:1]([CH2:3][C:4]([NH:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([C:36]([F:37])([F:39])[F:38])[CH:30]=1)([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:13])([F:14])[F:15])[CH:6]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:24])[F:25])[CH:17]=1)#[N:2].[N:2]1[NH:45][N:46]=[N:47][C:1]=1[CH2:3][C:4]([NH:27][C:28](=[O:40])[C:29]1[CH:34]=[CH:33][C:32]([F:35])=[C:31]([C:36]([F:38])([F:37])[F:39])[CH:30]=1)([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][C:12]([F:15])([F:13])[F:14])[CH:6]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:24])([F:25])[F:26])[CH:17]=1

Participants

6

Reactant 3

HCID 78378AzidotrimethylsilaneHCID 2724141Tetrabutylammonium FluorideHCID 59458463HCID 59458463, compound

Product 2

HCID 23582027HCID 23582027, compoundYield 72%HCID 59458463HCID 59458463, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

N-(2-cyano-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide was prepared as described in Procedure 11, 18, 6 and 7. LCMS: RT=4.04 min [M+H] 581.16 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm). A mixture of N-(2-cyano-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide (70 mg, 0.12 mmol), TMSN3 (0.025 ml. 1.6 eq) and TBAF.3H2O (19 mg, 0.5 eq) was heated in a sealed tube at 110° C. for 24 h. After allowing to cool to rt, the residue was dissolved in CH2Cl2, and purified by ISCO flash chromatography (silica gel, CH2Cl2/MeOH) to give N-(2-(2H-tetrazol-5-yl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)-4-fluoro-3-(trifluoromethyl)benzamide (Example 280, 54 mg, yield: 72%). LCMS: RT=3.91 min [M+H] 624.06, [M+Na] 647.06 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm).

Workup

  1. washLCMS: RT=4.04 min [M+H] 581.16 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm)
  2. temperatureto cool to rt
  3. custompurified by ISCO flash chromatography (silica gel, CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-d2aef141a730488fbd28ebd3753ef8f9
Source dataset
uspto-grants-2014_02
Patent number
US08642576B2

Reaction notes

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