HCID 59192802, compound → HCID 59192802, compound

HRID 1952408Notes

Reaction equation

HRID 1952408 reaction equation
[CH3:1][C:2]1[O:6][N:5]=[C:4]([CH2:7][C:8]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:32])([F:31])[F:30])[CH:23]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:21])([F:20])[F:19])[CH:12]=2)[C:9]#[N:10])[CH:3]=1>C1COCC1>[CH3:1][C:2]1[O:6][N:5]=[C:4]([CH2:7][C:8]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:31])([F:30])[F:32])[CH:23]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:19])([F:21])[F:20])[CH:12]=2)[C:9]#[N:10])[CH:3]=1.[CH3:1][C:2]1[O:6][N:5]=[C:4]([CH2:7][C:8]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][C:29]([F:31])([F:30])[F:32])[CH:23]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:19])([F:21])[F:20])[CH:12]=2)[CH2:9][NH2:10])[CH:3]=1

Participants

4

Reactant 1

HCID 59192802HCID 59192802, compound

Product 2

HCID 59192802HCID 59192802, compoundYield 94%HCID 59192816HCID 59192816, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

3-(5-Methylisoxazol-3-yl)-2,2-bis(3-(trifluoromethoxy)phenyl)-propanenitrile (476 mg, 94% yield) was prepared as described in Example 10 (Procedure 13 and 14). LCMS: RT=2.05 min [M+H] 456.97 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm); HPLC: RT=4.113 min (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm). To a solution of 3-(5-methylisoxazol-3-yl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanenitrile (0.172 g, 3.77 mmol) in THF was added BH3 (1.0 M in THF, 1.5 ml, 9.05 mmol) and the reaction was heated at 70° C. for 2 h. The reaction mixture was quenched with 1N HCl and the pH was adjusted to pH>10 by addition of 4N NaOH. The aqueous portion was extracted with EtOAc (3×30 mL). The combined organic portions were washed with water, sat. NaCl, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to yield 3-(5-methylisoxazol-3-yl)-2,2-bis(3-(trifluoromethoxy)phenyl)propan-1-amine as a clear oil (112 mg, 65% yield) which was used without further purification. LCMS: RT=1.78 min [M+H] 461.1 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm.

Workup

  1. washLCMS: RT=2.05 min [M+H] 456.97 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm)
  2. washHPLC: RT=4.113 min (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.2% PPA; 4 mL/min, monitoring at 220 nm)
  3. customThe reaction mixture was quenched with 1N HCl
  4. additionthe pH was adjusted to pH>10 by addition of 4N NaOH
  5. extractionThe aqueous portion was extracted with EtOAc (3×30 mL)
  6. washThe combined organic portions were washed with water, sat. NaCl
  7. dry with materialdried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e8c7ca61bd134c2c90cd611c42fc4754
Source dataset
uspto-grants-2013_03
Patent number
US08404896B2

Reaction notes

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