Dimethylacetamide → tert-butyl {(2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-yl}carbamate

HRID 715744Notes

Reaction equation

HRID 715744 reaction equation
CN(C)C(=O)C.C1(S([O-])(=O)=O)C=CC=CC=1.[CH3:17][S:18]([N:21]1[CH:25]=[C:24]2[CH2:26][NH2+:27][CH2:28][C:23]2=[N:22]1)(=[O:20])=[O:19].[C:29]([O:33][C:34](=[O:51])[NH:35][C@H:36]1[CH2:41][C:40](=O)[CH2:39][O:38][C@@H:37]1[C:43]1[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:44]=1[F:50])([CH3:32])([CH3:31])[CH3:30].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O>[F:50][C:44]1[CH:45]=[CH:46][C:47]([F:49])=[CH:48][C:43]=1[C@@H:37]1[C@@H:36]([NH:35][C:34](=[O:51])[O:33][C:29]([CH3:31])([CH3:30])[CH3:32])[CH2:41][C@@H:40]([N:27]2[CH2:26][C:24]3[C:23](=[N:22][N:21]([S:18]([CH3:17])(=[O:19])=[O:20])[CH:25]=3)[CH2:28]2)[CH2:39][O:38]1

Participants

6

Reactant 4

HCID 31374DimethylacetamideHCID 5049666Sodium triacetoxyborohydrideHCID 441939251,1-Dimethylethyl N-[(2R,3S)-2-(2,5-difluorophenyl)tetrahydro-5-oxo-2H-pyran-3-yl]carbamateHCID 140636156HCID 140636156, compound

Product 1

HCID 71486978tert-butyl {(2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-yl}carbamate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
5 °C

Procedure

A vessel was charged with N,N-dimethylacetamide (520.6 kg), 2-(methylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-5-ium benzenesulfonate (30.0 kg, 86.8 mol), and tert-butyl[(2R,3S)-2-(2,5-difluorophenyl)-5-oxotetrahydro-2H-pyran-3-yl]carbamate (131.2 kg, 95.3 mol). After dissolving at room temperature, the solution was cooled to 0-10° C. and sodium triacetoxyborohydride (24 kg, 113 mol) was added in four equal portions every 40 min. The reaction was then allowed to warm to room temperature and stirred an additional 5 h. The solution was then cooled to 5-15° C. and water (672 kg) was added over 1-2 h. The resulting slurry was filtered and the cake washed sequentially with N,N-dimethylacetamide, twice with water, and then n-heptane. The solids were dried to give tert-butyl {(2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-yl}carbamate.

Workup

  1. dissolutionAfter dissolving at room temperature
  2. temperatureto warm to room temperature
  3. temperatureThe solution was then cooled to 5-15° C.
  4. filtrationThe resulting slurry was filtered
  5. washthe cake washed sequentially with N,N-dimethylacetamide, twice with water
  6. customThe solids were dried

Sources & evidence

ORD record
ord-9f988292433b4d2fb694579c77550d4d
Source dataset
uspto-grants-2015_11
Patent number
US09187488B2

Reaction notes

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