Tetrahydrofuran → 5-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-amino}-tetrazol-2-yl-ethanol

HRID 2075061Notes

Reaction equation

[CH:1]1([CH:7]([O:50][CH3:51])[C:8]2[CH:45]=[CH:44][C:43]([C:46]([F:49])([F:48])[F:47])=[CH:42][C:9]=2[CH2:10][N:11]([CH2:27][C:28]2[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=2)[C:12]2[N:13]=[N:14][N:15](CCO[Si](C(C)(C)C)(C)C)[N:16]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C1C[O:73][CH2:72][CH2:71]1>>[F:37][C:34]([F:35])([F:36])[C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([C:38]([F:39])([F:41])[F:40])[CH:31]=1)[CH2:27][N:11]([CH2:10][C:9]1[CH:42]=[C:43]([C:46]([F:47])([F:48])[F:49])[CH:44]=[CH:45][C:8]=1[CH:7]([CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[O:50][CH3:51])[C:12]1[N:13]=[N:14][N:15]([CH:72]([OH:73])[CH3:71])[N:16]=1

Participants

Reactant 3

HCID 8028Tetrahydrofuran2×

HCID 2724141Tetrabutylammonium Fluoride

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

Product 1

HCID 866150515-{(3,5-Bis-trifluoromethyl-benzyl)-[2-(cyclohexyl-methoxy-methyl)-5-trifluoromethyl-benzyl]-amino}-tetrazol-2-yl-ethanolYield 89%

Procedure

To N-(2-(cyclohexyl(methoxy)methyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-(2-(tert-butyldimethylsilyloxy)ethyl)-2H-tetrazol-5-amine (39.3 mg, 0.052 mmol) in THF (0.3 mL) at room temperature was added TBAF in THF (1.0 M, 0.1 mL, 0.1 mmol). The mixture was stirred at room temperature overnight. Solvent was removed and the residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-50% ethyl acetate in heptane) to afford a colorless oil (29.5 mg, 89%). 1H NMR (400 MHz, CDCl3) δ ppm 0.94-1.13 (m, 5H) 1.17 (d, J=11.20 Hz, 1H) 1.43-1.53 (m, 1H) 1.60 (s, 2H) 1.67-1.74 (m, J=2.90 Hz, 1H) 1.91 (d, J=12.86 Hz, 1H) 2.35-2.42 (m, 1H) 3.06 (s, 3H) 4.08 (d, J=7.05 Hz, 1H) 4.12-4.16 (m, J=5.39 Hz, 2H) 4.62 (t, J=4.98 Hz, 2H) 4.72 (s, 2H) 4.75 (d, J=16.18 Hz, 1H) 4.88 (d, J=16.18 Hz, 1H) 7.36 (s, 1H) 7.49 (d, J=7.88 Hz, 1H) 7.56 (d, J=8.30 Hz, 1H) 7.67 (s, 2H) 7.78 (s, 1H). MS (ES+) Calc: 639.2, Found: 640.5 (M+1).

Workup

customSolvent was removed
customthe residue was purified by chromatography over 12+S Biotage silica column (eluted with 0-50% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-23a8d52406e94d3bb6ecd5d1caeaaf4d
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919506B2

Reaction notes

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