Hydrochloric Acid → 2-Hydroxy-2-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)acetonitrile

HRID 1506486Notes

Reaction equation

HRID 1506486 reaction equation
[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[S:17][C:18]4[C:28]5[C:23](=[CH:24][C:25]([CH:29]=[O:30])=[CH:26][CH:27]=5)[CH2:22][CH2:21][C:19]=4[N:20]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([C:35]#[N:36])(C)C.Cl>ClCCl.[I-].[Zn+2].[I-]>[OH:30][CH:29]([C:25]1[CH:24]=[C:23]2[C:28](=[CH:27][CH:26]=1)[C:18]1[S:17][C:16]([C:10]3[O:9][N:8]=[C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[C:11]=3[C:12]([F:15])([F:14])[F:13])=[N:20][C:19]=1[CH2:21][CH2:22]2)[C:35]#[N:36]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 82115Trimethylsilyl cyanideHCID 866699012-(3-Phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazole-7-carbaldehyde

Product 1

HCID 866699262-Hydroxy-2-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)acetonitrileYield 99.5%

Reagents, catalysts & solvents 2

HCID 9883512zinc(II)iodideCatalystHCID 6344DichloromethaneSolvent

Procedure

To 2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazole-7-carbaldehyde (Preparation 84A, 0.175 g, 0.410 mmol) in dichloromethane (5 mL) was added zinc iodide (0.039 g, 0.123 mmol) followed by trimethylsilyl cyanide (0.083 mL, 0.616 mmol) over a period of 1 min. at room temperature. The reddish-brown reaction mixture was stirred at room temperature for 1 h. The reaction mixture was cooled to 0° C. and conc. HCl (0.068 mL, 0.821 mmol) was added over a period of 1 min. and the contents stirred at room temperature for 5 min. The reaction mixture was partitioned between dichloromethane (2×20 mL) and 10% aq. Na2S2O3 (10 mL). The dichloromethane layer was dried over sodium sulfate and concentrated to yield 2-hydroxy-2-(2-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-4,5-dihydronaphtho[2,1-d]thiazol-7-yl)acetonitrile (0.185 g, 0.408 mmol, 99% yield) as a yellow solid. LC/MS M+1=454.

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. stirringthe contents stirred at room temperature for 5 min
  3. customThe reaction mixture was partitioned between dichloromethane (2×20 mL) and 10% aq. Na2S2O3 (10 mL)
  4. dry with materialThe dichloromethane layer was dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c5b6263bb4ea4eba8d4fa2ca531267ea
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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