Dimethyl Sulfide → Ammonia methanol

HRID 928211Notes

Reaction equation

HRID 928211 reaction equation
[C:1]([O:5]C([N:8]1[CH2:15][C@:14]2([F:16])[C@@H:10]([C:11](=O)[N:12]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]2=O)[CH2:9]1)=O)(C)(C)C.S(C)C>C1COCC1>[NH3:8].[CH3:1][OH:5].[CH2:18]([N:12]1[CH2:13][C@:14]2([F:16])[C@@H:10]([CH2:9][NH:8][CH2:15]2)[CH2:11]1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

Participants

5

Reactant 2

HCID 1068Dimethyl SulfideHCID 118081955HCID 118081955, compound

Product 2

HCID 21705897Ammonia methanolHCID 131735058HCID 131735058, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

(+/−)-cis-tert-Butyl-5-benzyl-3a-fluoro-4,6-dioxohexahydropyrrolo[3,4-c]pyrrole-2(1H)-carboxylate (160 mg, 0.459 mmol) was dissolved in THF (4.5 mL), and BH3.Me2S (0.174 mL, 1.84 mmol, 4.00 eq) was added at ambient temperature. The reaction mixture was stirred at 55° C. for 1.5 hr. A light slurry was formed during the reaction. The reaction was then cooled to 0° C. and quenched with dry MeOH (2 mL) dropwise followed by concentrated HCl until pH=4. The reaction solution was stirred at 0-10° C. for 1 hr. The temperature was raised to 55° C. for 1.5 hr was then cooled to rt and stirred for 20 hr. The reaction mixture was concentrated under reduced pressure, diluted with MeOH, neutralized by passing through an SCX column with MeOH and then 7 N NH3/MeOH and obtained the free amine. The title product was carried forward without further purification (100 mg, crude) m/z (APCI+) for C13H17FN2 221.25 (M+H)+.

Workup

  1. customA light slurry was formed during the reaction
  2. temperatureThe reaction was then cooled to 0° C.
  3. customquenched with dry MeOH (2 mL)
  4. stirringThe reaction solution was stirred at 0-10° C. for 1 hr
  5. temperatureThe temperature was raised to 55° C. for 1.5 hr
  6. temperaturewas then cooled to rt
  7. stirringstirred for 20 hr
  8. concentrationThe reaction mixture was concentrated under reduced pressure
  9. additiondiluted with MeOH

Sources & evidence

ORD record
ord-20c971b98da240b8b6d10c8de2933e49
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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