4-(Trifluoromethyl)benzenesulfonyl chloride → HCID 178527338, compound

HRID 1011615Notes

Reaction equation

HRID 1011615 reaction equation
[CH:1]1([C@@H:4]2[C:11]3[C:7](=[N:8][NH:9][CH:10]=3)[CH:6]([CH2:12][OH:13])[NH:5]2)[CH2:3][CH2:2]1.[F:14][C:15]([F:27])([F:26])[C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>N1C=CC=CC=1.C(Cl)Cl>[CH:1]1([C@@H:4]2[C:11]3[C:7](=[N:8][NH:9][CH:10]=3)[CH:6]([CH2:12][OH:13])[N:5]2[S:22]([C:19]2[CH:18]=[CH:17][C:16]([C:15]([F:14])([F:26])[F:27])=[CH:21][CH:20]=2)(=[O:24])=[O:23])[CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 27773994-(Trifluoromethyl)benzenesulfonyl chlorideHCID 178519992HCID 178519992, compound

Product 1

HCID 178527338HCID 178527338, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

((4R)-4-cyclopropyl-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-6-yl)methanol (36) (627 mg, 3.50 mmol) and 4-trifluoromethylbenzenesulfonyl chloride (2.57 g, 10.5 mmol) were dissolved in pyridine (5 mL) and the resulting mixture was stirred at rt for 12 h. The reaction mixture was diluted with CH2Cl2 (10 mL) and washed with 1 N aq. HCl (10 mL). The aq. phase was separated and extracted once with CH2Cl2 (10 mL) and the combined organic phases were then dried (Na2SO4), filtered and concentrated under vacuum. The residue was dissolved in THF (5 mL) and 3 N aq. NaOH (3.5 mL) was added. The resulting mixture was stirred at rt for 18 h and was subsequently extracted with EtOAc. The organic phase was then dried (Na2SO4), filtered, concentrated under vacuum and purified by preparative HPLC to give ((4R)-4-cyclopropyl-5-(4-(trifluoromethyl)phenylsulfonyl)-2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-6-yl)methanol (37) as a white solid. Retention time (min)=5.573, method [7], MS (m/z) 410.0 (M+Na)+.

Workup

  1. washwashed with 1 N aq. HCl (10 mL)
  2. customThe aq. phase was separated
  3. extractionextracted once with CH2Cl2 (10 mL)
  4. dry with materialthe combined organic phases were then dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. dissolutionThe residue was dissolved in THF (5 mL)
  8. addition3 N aq. NaOH (3.5 mL) was added
  9. stirringThe resulting mixture was stirred at rt for 18 h
  10. extractionwas subsequently extracted with EtOAc
  11. dry with materialThe organic phase was then dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum
  14. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-b58e652cd10e4e439ec82341cfebf6d9
Source dataset
uspto-grants-2011_07
Patent number
US07977368B2

Reaction notes

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