Diethyl dithiophosphate, potassium salt → Methyl 5-carbamothioyl-4-cyclobutyl-2-methylbenzoate

HRID 1487944Notes

Reaction equation

HRID 1487944 reaction equation
[C:1]([C:3]1[C:4]([CH:14]2[CH2:17][CH2:16][CH2:15]2)=[CH:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:2].P(OCC)(OCC)([S-])=[S:19]>O>[C:1]([C:3]1[C:4]([CH:14]2[CH2:15][CH2:16][CH2:17]2)=[CH:5][C:6]([CH3:13])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])(=[S:19])[NH2:2]

Participants

4

Reactant 2

HCID 1385274Diethyl dithiophosphate, potassium saltHCID 68288299Methyl 5-cyano-4-cyclobutyl-2-methylbenzoate2×

Product 1

HCID 86672531Methyl 5-carbamothioyl-4-cyclobutyl-2-methylbenzoateYield 78%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a round-bottom flask was added methyl 5-cyano-4-cyclobutyl-2-methylbenzoate (compound 6.4, 3.63 g, 0.015 mol), O,O′-diethyl dithiophosphate (10 mL) and water (1 mL). The reaction mixture was heated to 80° C. for 3 hours (CAUTION: significant gas evolution occurs—this and all other reactions described herein should be carried out in well ventilated fume hoods). After cooling to room temperature, the reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL). The organic layer was washed successively with saturated aqueous NaHCO3 (50 mL) and brine (50 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by silica gel flash chromatography (hexanes/ethyl acetate=80/20 to 50/50) to yield the title compound as a yellow solid (3.06 g, 78% yield). m/z (ES+) 264 (M+H)+. 1H NMR (400 MHz, CDCl3): δ 7.93 (s, 1H), 7.82 (s, 1H), 7.26 (s, 1H), 6.92 (s, 1H), 4.19 (m, 1H), 3.89 (s, 3H), 2.64 (s, 3H), 2.40 (m, 2H), 2.29-2.15 (m, 2H), 2.12-2.00 (m, 1H), 1.95-1.84 (m, 1H).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe reaction mixture was partitioned between ethyl acetate (50 mL) and water (50 mL)
  3. washThe organic layer was washed successively with saturated aqueous NaHCO3 (50 mL) and brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by silica gel flash chromatography (hexanes/ethyl acetate=80/20 to 50/50)

Sources & evidence

ORD record
ord-aee4d64d35dd4c0892f047d083aef708
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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