Hydrochloric Acid → HCID 58968605, compound

HRID 2075044Notes

Reaction equation

HRID 2075044 reaction equation
[F:1][C:2]([F:42])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:36]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH3:25])=[CH:17][C:16]=1[C:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)=[O:27])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1.[CH3:43][Mg]Br.Cl.C(OCC)(=O)C>C1COCC1>[F:42][C:2]([F:1])([F:41])[C:3]1[CH:4]=[C:5]([CH:34]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:36]=1)[CH2:6][N:7]([CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH3:25])=[CH:17][C:16]=1[C:26]([CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1)([OH:27])[CH3:43])[C:8]1[N:9]=[N:10][N:11]([CH3:13])[N:12]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 58968652HCID 58968652, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 58968605HCID 58968605, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2-(((3,5-bis(trifluoromethyl)benzyl)(2-methyl-2H-tetrazol-5-yl)amino)methyl)-5-methyl-4-(trifluoromethyl)phenyl)(cyclohexyl)methanone (52 mg, 0.085 mmol) in anhydrous THF (10 mL) under nitrogen at 0° C. was added methylmagnesium bromide (3.0 M solution in THF, 25.6 mg, 0.114 mL, 0.342 mmol). The solution was stirred at 0° C. for 30 minutes, then warmed to room temperature and stirred for 1.5 hours. The solution was then poured into a mixture of 2 N hydrochloric acid (10 mL) and ethyl acetate (20 mL). The solution was stirred at room temperature for 10 minutes then the layers were separated and the aqueous layer was extracted with ethyl acetate (3×15 mL). The combined organics layer was dried with anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography on a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 1-50% ethyl acetate in heptane) to yield the title compound (97.2%). 1H NMR (400 MHz, CDCl3) δ 7.73 (s, 1H) 7.68 (s, 2H) 7.33 (s, 1H) 7.17 (s, 1H) 5.39 (d, J=16.17 Hz, 1H) 4.82 (d, J=15.76 Hz, 1H) 4.77(s, 2H) 4.15(s, 3H) 2.39 (s, 3H) 1.62 (m, 6H) 1.24 (s, 3H) 1.04 (m, 5H). LC-MS calc. 623.5, found 624.6 (M+H)

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for 1.5 hours
  3. stirringThe solution was stirred at room temperature for 10 minutes
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×15 mL)
  6. dry with materialThe combined organics layer was dried with anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by flash chromatography on a 4 g RediSep column (Teledyne Isco Inc., Lincoln Nebr.) (eluted with 1-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-201ae5e8d43f473c8e0d60b4abaa2b9f
Source dataset
uspto-grants-2011_04
Patent number
US07919506B2

Reaction notes

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