Methanol → tert-Butyl 2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate

HRID 340756Notes

Reaction equation

HRID 340756 reaction equation
O[C:2]12[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH:6]1[CH:5]=[N:4][NH:3]2.CO.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C([O-])(O)=O.[Na+]>ClCCl>[NH:3]1[C:2]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][C:6]=2[CH:5]=[N:4]1

Participants

6

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 711530161,1-Dimethylethyl 3a,4,6,6a-tetrahydro-6a-hydroxypyrrolo[3,4-c]pyrazole-5(1H)-carboxylate

Product 1

HCID 7147072tert-Butyl 2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 6a-hydroxy-3a,4,6,6a-tetrahydropyrrol[3,4-c]pyrazole-5(1H)-carboxylate (47.0 kg, 207 mol) in dichloromethane (669 kg) at 0° C. was added a methanol solution of toluene-4-sulfonic acid monohydrate (3.7 kg, 20 mol in 38 kg MeOH) drop-wise over 2 h. The reaction was then aged for 4 h at this temperature. Then, 5% aqueous NaHCO3 (91 kg) was added and stirred at room temperature for 30 min. The layers were then separated and the aqueous extracted with dichloromethane (312 kg). The combined organics were washed with 5% brine (190 kg then 483 kg), treated with activated carbon (2.7 kg) and filtered. The resulting organics were dried with Na2SO4, filtered, and concentrated to 71-118 L. n-Heptane was then added (238 kg) and the batch further concentrated to 188-235 L. The slurry was cooled to 10-20° C., filtered, and the cake washed with n-heptane. The solids were dried under vacuum at 40-50° C. overnight to give tert-butyl 4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate.

Workup

  1. customThe layers were then separated
  2. extractionthe aqueous extracted with dichloromethane (312 kg)
  3. washThe combined organics were washed with 5% brine (190 kg
  4. addition483 kg), treated with activated carbon (2.7 kg)
  5. filtrationfiltered
  6. dry with materialThe resulting organics were dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to 71-118 L
  9. additionn-Heptane was then added (238 kg)
  10. concentrationthe batch further concentrated to 188-235 L
  11. temperatureThe slurry was cooled to 10-20° C.
  12. filtrationfiltered
  13. washthe cake washed with n-heptane
  14. customThe solids were dried under vacuum at 40-50° C. overnight

Sources & evidence

ORD record
ord-862de41ad88940aea7ea175917048053
Source dataset
uspto-grants-2014_11
Patent number
US08895603B2

Reaction notes

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