Diisopropylethylamine → (3R)-3-Methyl-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine hydrochloride

HRID 517763Notes

Reaction equation

HRID 517763 reaction equation
Cl.[CH3:2][C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][NH:4]1.[Cl:9][CH2:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[CH:17]=2)[N:14]=[N:13][N:12]=1.C(N(C(C)C)CC)(C)C>C(#N)C>[ClH:9].[CH3:2][C@@H:3]1[CH2:8][O:7][CH2:6][CH2:5][N:4]1[CH2:10][C:11]1[N:15]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:24])([F:23])[F:25])[CH:17]=2)[N:14]=[N:13][N:12]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 80271755-(Chloromethyl)-1-(3-(trifluoromethyl)phenyl)-1H-tetrazoleHCID 57356922(3R)-3-Methylmorpholine hydrochloride

Product 1

HCID 86691891(3R)-3-Methyl-4-({1-[3-(trifluoromethyl)phenyl]-1H-tetrazol-5-yl}methyl)morpholine hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of (3R)-3-methylmorpholine hydrochloride (52.4 mg, 0.381 mmol), 5-(chloromethyl)-1-[3-(trifluoromethyl)phenyl]-1H-tetrazole (50 mg, 0.190 mmol, commercially available from Otava, Kiev, Ukraine) and di-isopropylethylamine (0.067 mL, 0.381 mmol) in acetonitrile (1.5 mL) was heated to 120° C. for 15 minutes in a microwave reactor. The reaction mixture was allowed to cool and the solvent removed under vacuum. The residue was purified by MDAP and fractions containing the desired product were combined and the solvent removed. The residue was dissolved in a minimum of diethyl ether before the dropwise addition of 1N HCl in diethyl ether (3 mL) leading to precipitation. The solvent was removed under a stream of argon and the residue triturated with diethyl ether then dried under vacuum to yield the title compound as a white solid (46 mg).

Workup

  1. temperatureto cool
  2. customthe solvent removed under vacuum
  3. customThe residue was purified by MDAP and fractions
  4. additioncontaining the desired product
  5. customthe solvent removed
  6. dissolutionThe residue was dissolved in a minimum of diethyl ether before the dropwise addition of 1N HCl in diethyl ether (3 mL)
  7. customleading to precipitation
  8. customThe solvent was removed under a stream of argon
  9. customthe residue triturated with diethyl ether
  10. customthen dried under vacuum

Sources & evidence

ORD record
ord-2e2cb11d0a8547538000865dc27a56e4
Source dataset
uspto-grants-2015_08
Patent number
US09115132B2

Reaction notes

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