Hydrochloric Acid → HCID 86716594, compound

HRID 929905Notes

Reaction equation

HRID 929905 reaction equation
C([O:5][C:6]([C@:8]1([NH:30]C(OC(C)(C)C)=O)[CH2:13][C@@H:12]([S:14][C:15]2[NH:19][C:18]([CH:20]([F:22])[F:21])=[N:17][N:16]=2)[C@@H:11]2[C@H:9]1[C@H:10]2[C:23]([O:25]C(C)(C)C)=[O:24])=[O:7])(C)(C)C.[ClH:38]>O1CCOCC1>[ClH:38].[NH2:30][C@@:8]1([C:6]([OH:7])=[O:5])[CH2:13][C@@H:12]([S:14][C:15]2[N:19]=[C:18]([CH:20]([F:21])[F:22])[NH:17][N:16]=2)[C@@H:11]2[C@H:9]1[C@H:10]2[C:23]([OH:25])=[O:24]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178452939HCID 178452939, compound

Product 1

HCID 86716594HCID 86716594, compoundYield 93%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Add ditert-butyl(1R,2S,4R,5R,6R)-2-(tert-butoxycarbonylamino)-4-[[5-(difluoromethyl)-4H-1,2,4-triazol-3-yl]sulfanyl]bicyclo[3.1.0]hexane-2,6-dicarboxylate (0.356 g, 651.3 μmol) in 1,4-dioxane (1.63 mL) to a solution of hydrogen chloride (4M in dioxane). Heat the mixture to 50° C. with stirring. A solid precipitate out of solution soon after heating commenced. Cool the reaction mixture and concentrate under reduced pressure. Purify the residue by silica gel chromatography (40 g SiO2) eluting with 0-20% hydrochloric acid (0.01 M aqueous) in acetonitrile gradient over 60 minutes at 40 mL/minute flow rate. Concentrate under reduced pressure to provide the crude material as oil. Re-purify using same conditions. Concentrate under reduced pressure to give the title compound as a white solid (0.196 g, 93%). MS (m/z): 335 (M+1).

Workup

  1. temperatureA solid precipitate out of solution soon after heating
  2. temperatureCool the reaction mixture
  3. concentrationconcentrate under reduced pressure
  4. customPurify the residue by silica gel chromatography (40 g SiO2)
  5. washeluting with 0-20% hydrochloric acid (0.01 M aqueous) in acetonitrile gradient over 60 minutes at 40 mL/minute flow rate
  6. concentrationConcentrate under reduced pressure
  7. customto provide the crude material as oil
  8. concentrationConcentrate under reduced pressure

Sources & evidence

ORD record
ord-82fbaf83328c408bbd53fbf51b47281f
Source dataset
uspto-grants-2016_03
Patent number
US09296710B2

Reaction notes

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