Hydrochloric Acid → 4-(2-(((3,5-Bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile

HRID 2075110Notes

Reaction equation

HRID 2075110 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.[H-].[Na+].Br[CH2:26][C:27]1[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[CH:29][C:28]=1[C:37]1([O:45][CH3:46])[CH2:42][CH2:41][CH:40]([C:43]#[N:44])[CH2:39][CH2:38]1.Cl>C1COCC1.O>[F:18][C:17]([F:19])([F:20])[C:15]1[CH:14]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:16]=1)[CH2:6][N:7]([CH2:26][C:27]1[CH:32]=[C:31]([C:33]([F:34])([F:35])[F:36])[CH:30]=[CH:29][C:28]=1[C:37]1([O:45][CH3:46])[CH2:38][CH2:39][CH:40]([C:43]#[N:44])[CH2:41][CH2:42]1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydride2×HCID 230732215-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazoleHCID 589686484-(2 (Bromomethyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile

Product 1

HCID 589686304-(2-(((3,5-Bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrileYield 119.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazole-5-amine (285 mg, 0.877 mmol) in anhydrous THF (5 mL) was added sodium hydride (60% dispersion in mineral oil, 105 mg, 2.63 mol) and the mixture was stirred for 5 minutes then a solution of 4-(2 (bromomethyl)-4-(trifluoromethyl)phenyl)-4-methoxycyclohexanecarbonitrile (330 mg, 0.877 mmol) in anhydrous THF (5 mL) was added. A further aliquot of sodium hydride (52 mg, 1.3 mmol) was added. The solution was stirred at room temperature for 72 hours. Water and 2 N HCl (5 mL) were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organics were dried with anhydrous sodium sulfate and concentrated under reduced pressure to give a yellow oil (0.65 gm). This material was initially purified by flash chromatography on a 40 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 5-75% ethyl acetate in heptane) and finally purified on 1 mm silica gel rotor (Chromatotron, Harrison Research) (eluted with 20-70% dichloromethane in heptane) to yield the title compound as a colorless foam (134 mg, 24.6%). 1H NMR (400 MHz, CDCl3) δ 7.74 (s, H) 7.67(s, 2H) 7.44 (d, J=5.81 Hz, 2H) 7.29 (d, J=8.72 Hz, 1H) 5.01 (s, 2H) 4.76 (s, 2H) 4.15 (s, 3H) 2.87(s, 3H) 2.43(m, 1H) 2.20(d, J=12.45 Hz, 2H) 1.99(m, 2H) 1.55(m, 4H). LC-MS calc. 620, found 621.5 (M+H)

Workup

  1. stirringThe solution was stirred at room temperature for 72 hours
  2. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organics were dried with anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-cf93bceea5354e0aaa45613e0f76dc41
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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