Sodium Carbonate → N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(2-(tert-butyldimethylsilyloxy)ethyl)-2H-tetrazol-5-amine

HRID 2075060Notes

Reaction equation

HRID 2075060 reaction equation
[CH:1]1([CH:7]([O:40][CH3:41])[C:8]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:9]=2[CH2:10][N:11]([CH2:17][C:18]2[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[C:20]([C:28]([F:31])([F:30])[F:29])[CH:19]=2)[C:12]2[N:13]=[N:14][NH:15][N:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:43][CH2:44][O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47].C(=O)([O-])[O-].[Na+].[Na+]>CC1OCCC1.CN(C=O)C>[CH:1]1([CH:7]([O:40][CH3:41])[C:8]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][C:9]=2[CH2:10][N:11]([CH2:17][C:18]2[CH:19]=[C:20]([C:28]([F:29])([F:31])[F:30])[CH:21]=[C:22]([C:24]([F:25])([F:26])[F:27])[CH:23]=2)[C:12]2[N:13]=[N:14][N:15]([CH2:43][CH2:44][O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[N:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 58968733N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2H-tetrazol-5-amine

Product 1

HCID 58968743N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(2-(tert-butyldimethylsilyloxy)ethyl)-2H-tetrazol-5-amineYield 77%

Reagents, catalysts & solvents 1

HCID 1185110082-MeTHF DMFSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2H-tetrazol-5-amine (40.4 mg, 0.068 mmol) and (2-bromoethoxy)(tert-butyl)dimethylsilane (25 mg, 22 μL, 0.10 mmol) in 2-MeTHF/DMF was added sodium carbonate (29.1 mg, 0.275 mmol). The slurry was stirred at 60° C. overnight. The reaction was diluted and filtered. The filtrate was concentrated and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20% ethyl acetate in heptane) to afford the title compound (39.3 mg, 77%). 1H NMR (400 MHz, CDCl3) δ ppm 0.08 (s, 6H) 0.80 (s, 9H) 0.92-1.12 (m, 5H) 1.15-1.21 (m, 1H) 1.42-1.52 (m, 1H) 1.57-1.62 (m, 2H) 1.68-1.72 (m, J=2.90 Hz, 1H) 1.89 (d, J=12.44 Hz, 1H) 3.03 (s, 3H) 4.05-4.09 (m, 3H) 4.54 (t, J=5.60 Hz, 2H) 4.64-4.76 (m, 3H) 4.89 (d, J=16.17 Hz, 1H) 7.35 (s, 1H) 7.47 (d, J=7.88 Hz, 1H) 7.54 (d, J=9.12 Hz, 1H) 7.65 (s, 2H) 7.75 (s, 1H). MS (ES+) Calc: 753.3, Found: 754.6 (M+1).

Workup

  1. additionThe reaction was diluted
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customthe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-45cf5d64c8f942b08acb9ae5450b76be
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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