3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde → 1-(3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethanol

HRID 1506542Notes

Reaction equation

HRID 1506542 reaction equation
[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH:25]=[O:26])=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:30])([F:29])[F:28])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:31][Mg]Br>C1COCC1>[C:1]1([C:7]2[O:11][N:10]=[C:9]([C:12]3[O:16][N:15]=[C:14]4[C:17]5[C:22]([CH2:23][CH2:24][C:13]=34)=[CH:21][C:20]([CH:25]([OH:26])[CH3:31])=[CH:19][CH:18]=5)[C:8]=2[C:27]([F:28])([F:29])[F:30])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 866698753-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehydeHCID 178418573HCID 178418573, compound2×

Product 1

HCID 671719831-(3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethanolYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

To 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazole-7-carbaldehyde (Preparation 88A, 0.425 g, 1.036 mmol) in THF (5 mL), cooled to −50° C. was added methylmagnesium bromide (3.0M in diethyl ether) (0.380 mL, 1.139 mmol) over a period of 2 min. The contents were allowed to come to room temperature over a period of 30 min. The reaction mixture was re-cooled to −50° C. and 0.15 mL of methylmagnesium bromide was added and the contents allowed to come to room temperature over a period of 10 min. The reaction mixture was quenched by the slow addition of sat. aq ammonium chloride (3 mL) and extracted into EtOAc (2×15 mL). The EtOAc layer was dried over sodium sulfate and concentrated to yield 1-(3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)-4,5-dihydronaphtho[1,2-c]isoxazol-7-yl)ethanol (0.44 g, 1.032 mmol, 100% yield) as a tan colored solid. LC/MS M+1=427.

Workup

  1. waitto come to room temperature over a period of 10 min
  2. customThe reaction mixture was quenched by the slow addition of sat. aq ammonium chloride (3 mL)
  3. extractionextracted into EtOAc (2×15 mL)
  4. dry with materialThe EtOAc layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7026c1aab97045459219698536c435e6
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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