Dimethylformamide → HCID 178452941, compound

HRID 2172992Notes

Reaction equation

HRID 2172992 reaction equation
C(=O)([O-])[O-].[K+].[K+].[NH:7]1[CH:11]=[N:10][C:9]([SH:12])=[N:8]1.CN(C)C=O.[C:18]([O:22][C:23]([NH:25][C@@:26]1([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:31]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=2)[C@H:30](OS(C)(=O)=O)[C@@H:29]2[C@H:27]1[C@H:28]2[C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[O:24])([CH3:21])([CH3:20])[CH3:19]>C(=O)(O)[O-].[Na+]>[C:18]([O:22][C:23]([NH:25][C@@:26]1([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[C@H:31]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([Cl:41])[CH:35]=2)[C@@H:30]([S:12][C:9]2[N:10]=[CH:11][NH:7][N:8]=2)[C@@H:29]2[C@H:27]1[C@H:28]2[C:47]([O:49][C:50]([CH3:52])([CH3:51])[CH3:53])=[O:48])=[O:24])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 86695975Di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylateHCID 178527894HCID 178527894, compound

Product 1

HCID 178452941HCID 178452941, compoundYield 69.5%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Procedure

Potassium carbonate (1.45 g, 10.50 mmol) is added to 1H-1,2,4-triazole-3-thiol (424.79 mg, 4.20 mmol) and dimethylformamide (10.50 mL, 9.93 g, 135.80 mmol) at room temperature and stirred. After 5 minutes, di-tert-butyl (1S,2R,3S,4R,5R,6R)-2-[(tert-butoxycarbonyl)amino]-3-[(3,4-dichlorobenzyl)oxy]-4-[(methylsulfonyl)oxy]bicyclo[3.1.0]hexane-2,6-dicarboxylate (1.40 g, 2.10 mmol) is added to the reaction and stirred at 85° C. After 2 days, cool the reaction to room temperature, dilute with saturated sodium bicarbonate, then extract with ethyl acetate (3×). The combined organics are washed with water, brine, filtered, and concentrated under reduced pressure to give a residue. The residue is purified by flash chromatography eluting with 5-75% ethyl acetate in hexanes to give the title compound (978.0 mg, 1.46 mmol, 69%). MS (m/z): 671/669 (M−1).

Workup

  1. stirringstirred at 85° C
  2. waitAfter 2 days
  3. temperaturecool
  4. customthe reaction to room temperature
  5. extractionextract with ethyl acetate (3×)
  6. washThe combined organics are washed with water, brine
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto give a residue
  10. customThe residue is purified by flash chromatography
  11. washeluting with 5-75% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-f93fde69b90e417981e051d479bf83ff
Source dataset
uspto-grants-2015_06
Patent number
US09056844B2

Reaction notes

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