Sodium hydride → HCID 58968664, compound

HRID 2075102Notes

Reaction equation

HRID 2075102 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+].[H][H].Br[CH2:28][C:29]1[CH:34]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:32]=[CH:31][C:30]=1[CH:39]([O:47][CH3:48])[C:40]1([CH3:46])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1.[Cl-].[Li+]>CN(C)C=O.O>[CH3:48][O:47][CH:39]([C:40]1([CH3:46])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1)[C:30]1[CH:31]=[CH:32][C:33]([C:35]([F:38])([F:37])[F:36])=[CH:34][C:29]=1[CH2:28][N:7]([CH2:6][C:5]1[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]=1)[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 433294Lithium ChlorideHCID 230732215-[N-(3',5'-Bistrifluoromethylbenzyl)amino]-2-methyltetrazoleHCID 67091385HCID 67091385, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 58968664HCID 58968664, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of the Step D product (210 mg, 0.665 mmol) and tetrabromomethane (231 mg, 0.7 mmol) in anhydrous dichloromethane (5 mL) under N2 at 0° C. was added powdered triphenylphosphine (192 mg, 0.73 mmol). After 90 minutes further aliquots of tetrabromomethane (23 mg, 0.07 mmol) and powdered triphenylphosphine (19 mg, 0.073 mmol) were added and the mixture stirred for 6 hours. The solvent was then removed under vacuum and the residue was purified by flash chromatography on a 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 0-50% ethyl acetate in heptane) to give 2-(bromomethyl)-1-(methoxy(1-methylcyclohexyl)methyl)-4-(trifluoromethyl)benzene (194 mg). To N-(3,5-bis(trifluoromethyl)benzyl)-2-methyl-2H-tetrazol-5-amine (Preparation 5, 216 mg, 0.66 mmol) was added sodium hydride (60% dispersion in mineral oil, 40 mg, 1 mmol), the air in the flask was replaced by nitrogen and anhydrous N,N-dimethylformamide (4 mL) was added. Hydrogen was evolved briskly and a yellow solution formed, darkening to orange-brown over 1 hour. A solution of 2-(bromomethyl)-1-(methoxy(1-methylcyclohexyl)methyl)-4-(trifluoromethyl)benzene (194 mg, 0.51 mmol) in anhydrous N,N-dimethylformamide (2×1 mL) was added. The mixture was stirred at room temperature for 16 hours, diluted with water containing lithium chloride and a little hydrochloric acid to give an acidic solution and the mixture extracted with dichloromethane (3×). The combined organic layers were dried over sodium sulfate and concentrated to dryness under vacuum. The residue was purified by flash chromatography on a 12 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 0-60% ethyl acetate in heptane) to yield the title compound as a colorless viscous oil (0.24 g). 1H NMR (400 MHz, CDCl3) δ7.79 (s, 1H), 7.65 (s, 2h), 7.65-7.51 (m, 2H), 7.37 (s, 1H), 5.06 (d, J=16 Hz, 1H), 4.79 (d, J=16.3 Hz, 1H), 4.61 (d, J=16.3 Hz, 1H), 4.61-4.51 (m, 1H), 4.22 (s, 3H), 4.10 (s, 1H), 2.98 (s, 3H), 1.65-1.56 (m, 1H), 1.56-1.18 (m, 7H), 1.17-0.98 (m, 2H), 0.88 (s, 3H).

Workup

  1. additionwas added
  2. customa yellow solution formed
  3. customorange-brown over 1 hour

Sources & evidence

ORD record
ord-15efef56e5da40e7838f377d862deca1
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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