5-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazole → N-(2-(1-methoxycyclohexyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine

HRID 2075100Notes

Reaction equation

HRID 2075100 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1)[CH2:6][NH:7][C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.CC(C)([O-])C.[K+].Br[CH2:30][C:31]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][C:32]=1[C:41]1([O:47][CH3:48])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1>O1CCCC1>[CH3:48][O:47][C:41]1([C:32]2[CH:33]=[CH:34][C:35]([C:37]([F:38])([F:40])[F:39])=[CH:36][C:31]=2[CH2:30][N:7]([CH2:6][C:5]2[CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:16]=[C:15]([C:17]([F:19])([F:20])[F:18])[CH:14]=2)[C:8]2[N:9]=[N:10][N:11]([CH3:13])[N:12]=2)[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46]1

Participants

5

Reactant 3

HCID 230732215-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazoleHCID 23665647Potassium tert-butoxideHCID 589687252-(Bromomethyl)-1-(1-methoxycyclohexyl)-4-(trifluoromethyl)benzene

Product 1

HCID 58968714N-(2-(1-methoxycyclohexyl)-5-(trifluoromethyl)benzyl)-N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amineYield 59.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (26 mg; 0.079 mmol) in tetrahydrofuran (0.3 mL) was added potassium t-butoxide (80 uL; 0.08 mmol; 1.0M in tetrahydrofuran). A solution of 2-(bromomethyl)-1-(1-methoxycyclohexyl)-4-(trifluoromethyl)benzene (25 mg; 0.071 mmol) in tetrahydrofuran (0.2 mL) was added. The reaction was stirred at room temperature for 3 hours. The reaction was quenched with 2 drops of water. The mixture was diluted with ethyl acetate and filtered through a column containing silica and sodium sulfate and concentrated. The residue was purified by 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-45% ethyl acetate in heptane) to give 25 mg (59%) of a colorless gum. MS (ES+): Calc: 595.5, Found: 596 (M+H). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (s, 1H), 7.73 (s, 2H), 7.48 (d, J=7.47 Hz, 2H), 7.42 (d, J=8.30 Hz, 1H), 5.14 (s, 2H), 4.79 (s, 2H), 4.20 (s, 3H), 2.92 (s, 3H), 2.12 (d, J=11.62 Hz, 2H), 1.77-1.52(m, 8H).

Workup

  1. customThe reaction was quenched with 2 drops of water
  2. additionThe mixture was diluted with ethyl acetate
  3. filtrationfiltered through a column
  4. additioncontaining silica and sodium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 10-45% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-d00c66c396ec422f83127a05ea83b733
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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