Diisopropylamine → (5-Benzyloxy-4-methoxy-2-methylphenyl)(2-chloro-4-trifluoromethyl-3-pyridyl)methanol

HRID 1835410Notes

Reaction equation

HRID 1835410 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.C([N-]C(C)C)(C)C.[Li+].[Cl:21][C:22]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][N:23]=1.[CH2:32]([O:39][C:40]1[C:41]([O:49][CH3:50])=[CH:42][C:43]([CH3:48])=[C:44]([CH:47]=1)[CH:45]=[O:46])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[Cl-].[NH4+].C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O1CCCC1.CCCCCC>[CH2:32]([O:39][C:40]1[C:41]([O:49][CH3:50])=[CH:42][C:43]([CH3:48])=[C:44]([CH:45]([C:27]2[C:22]([Cl:21])=[N:23][CH:24]=[CH:25][C:26]=2[C:28]([F:29])([F:30])[F:31])[OH:46])[CH:47]=1)[C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1

Participants

11

Reactant 7

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 1449582-Chloro-4-(trifluoromethyl)pyridineHCID 516892Sodium BicarbonateHCID 2724682Lithium diisopropylamideHCID 121515395-(Benzyloxy)-4-methoxy-2-methylbenzaldehydeHCID 178418339Butyllithium

Product 1

HCID 12151540(5-Benzyloxy-4-methoxy-2-methylphenyl)(2-chloro-4-trifluoromethyl-3-pyridyl)methanolYield 96%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-50 °C

Procedure

A hexane solution (11.4 ml) of n-butyllithium was dropwise added to a tetrahydrofuran (45 ml) solution of diisopropylamine (2.81 g) at 0° C., followed by stirring for 1 hour to prepare a tetrahydrofuran solution of lithium diisopropylamide. The solution was cooled to −50° C., and a tetrahydrofuran (7.5 ml) solution of 2-chloro-4-trifluoromethylpyridine (2.81 g) was gradually added thereto, followed by stirring at the same temperature for 30 minutes. The solution was cooled to −78° C., and a tetrahydrofuran (37.5 ml) solution of 5-benzyloxy-4-methoxy-2-methylbenzaldehyde (3.97 g) was gradually added thereto, followed by stirring at the same temperature for 1 hour. A saturated aqueous ammonium chloride solution (50 ml) was added thereto, the temperature was raised to room temperature, the mixture was poured into a saturated aqueous sodium bicarbonate solution (50 ml), and extraction with ethyl acetate (150 ml) was carried out twice. The ethyl acetate phase was washed with an aqueous sodium chloride solution (100 ml) and dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 6.48 g (yield 96%) of (5-benzyloxy-4-methoxy-2-methylphenyl)(2-chloro-4-trifluoromethyl-3-pyridyl)methanol as a red-yellow oily substance, and its structure was confirmed by nuclear magnetic resonance spectrum.

Workup

  1. stirringby stirring at the same temperature for 30 minutes
  2. temperatureThe solution was cooled to −78° C.
  3. stirringby stirring at the same temperature for 1 hour
  4. temperaturethe temperature was raised to room temperature
  5. washThe ethyl acetate phase was washed with an aqueous sodium chloride solution (100 ml)
  6. dry with materialdried over magnesium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-def2283ce1a043e89e7a6604b7cf6535
Source dataset
uspto-grants-2004_08
Patent number
US06770662B2

Reaction notes

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