Acetone → Methyl 4-cyano-5-(isopropylamino)-2-methylbenzoate

HRID 906160Notes

Reaction equation

HRID 906160 reaction equation
[NH2:1][C:2]1[C:3]([C:13]#[N:14])=[CH:4][C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].FC(F)(F)C(O)=O.[CH3:22][C:23]([CH3:25])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[C:13]([C:3]1[C:2]([NH:1][CH:23]([CH3:25])[CH3:22])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([CH3:12])[CH:4]=1)#[N:14]

Participants

6

Reactant 4

HCID 180AcetoneHCID 6422Trifluoroacetic acidHCID 5049666Sodium triacetoxyborohydrideHCID 67402842Methyl 5-amino-4-cyano-2-methylbenzoate

Product 1

HCID 67403235Methyl 4-cyano-5-(isopropylamino)-2-methylbenzoateYield 76.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

Methyl 5-amino-4-cyano-2-methylbenzoate (synthesized in reagent preparation 41, step 4) (240 mg, 1.26 mmol) was dissolved in 1,2-dichloroethane (7 mL) and was treated with trifluoroacetic acid (0.6 mL, 7.57 mmol), acetone (0.28 mL, 3.79 mmol), and sodium triacetoxyborohydride (802 mg, 3.78 mmol) at 45° C. for 20 min. The reaction mixture was cooled to ambient temperature and quenched with saturated aqueous sodium bicarbonate and was partitioned with dichloromethane. The aqueous portion was extracted with dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, then filtered and concentrated to afford a yellow oil which was purified by column chromatography (silica gel, 10% dichloromethane in hexanes) to afford methyl 4-cyano-5-(isopropylamino)-2-methylbenzoate (224 mg, 0.96 mmol, 76% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.25 (s, 1H), 7.16 (s, 1H), 4.28 (d, 1H), 3.91 (s, 3H), 3.77-3.74 (m, 1H), 2.40 (s, 3H), 1.27 (s, 3H), 1.26 (s, 3H); MS (EI) for C14H16N2O2: 233 (MH+).

Workup

  1. customquenched with saturated aqueous sodium bicarbonate
  2. customwas partitioned with dichloromethane
  3. extractionThe aqueous portion was extracted with dichloromethane
  4. washThe combined organic portion was washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a yellow oil which
  9. customwas purified by column chromatography (silica gel, 10% dichloromethane in hexanes)

Sources & evidence

ORD record
ord-5e85a1eb39394eaf884e270ed6ec4d7a
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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