Toluene → HCID 71737514, compound

HRID 1487464Notes

Reaction equation

HRID 1487464 reaction equation
[F:1][CH:2]([F:34])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[S:22][C:21]([CH:23]([NH:25]S(C(C)(C)C)=O)[CH3:24])=[N:20][CH:19]=3)=[CH:14][CH:13]=2)[O:7]C1(C)C)=[O:4].FC(F)(F)C(O)=O.C1(C)C=CC=CC=1>C(Cl)Cl.O>[NH2:25][CH:23]([C:21]1[S:22][C:18]([C:15]2[CH:14]=[CH:13][C:12]([C@@H:8]([OH:7])[C@H:9]([NH:5][C:3](=[O:4])[CH:2]([F:34])[F:1])[CH2:10][F:11])=[CH:17][CH:16]=2)=[CH:19][N:20]=1)[CH3:24]

Participants

6

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acidHCID 86695422HCID 86695422, compound

Product 1

HCID 71737514HCID 71737514, compoundYield 41.5%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(1-(5-(4-((4S,5R)-3-(2,2-difluoroacetyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)thiazol-2-yl)ethyl)-2-methylpropane-2-sulfinamide (315 mg, 0.6 mmol) in CH2Cl2 (25 mL) at 0° C. is added trifluoroacetic acid (5 mL) and 5 drops water. The reaction is allowed to warm to room temperature and stir for 1 hour. Toluene (20 mL) is added and contents are concentrated under vacuum. Toluene addition/concentration is repeated and contents are placed under high vacuum for 5 minutes. Methanol (25 mL) is added to the reaction flask and the solution is cooled in an ice bath. HCl in methanol (4 mL of 1.25 mL solution) is added and the reaction is allowed to warm to room temperature while stirring. After 2 hours, the reaction is concentrated under vacuum to ˜3 mL of solvent left and purified directly using reverse phase chromatography, eluting from 95:5 water/acetonitrile/0.1% trifluoroacetic acid to 95:5 acetonitrile/water/0.1% trifluoroacetic acid. The purified fractions are concentrated under vacuum to remove acetonitrile. The aqueous phase is diluted with saturated NaHCO3 (100 mL) and extracted with ethylacetate (2×100 mL). The combined organic phase is dried (Na2SO4) and concentrated under vacuum to afford the title compound (93 mg): 1H NMR (400 MHz, DMSO-d6) δ: 1.39 (d, 3H), 2.38 (m, 2H), 4.18-4.33 (m, 2.5H), 4.40-4.44 (m, 0.5H), 4.52-4.56 (m, 0.5H), 4.64-4.67 (m, 0.5H), 4.85 (t, 1H), 5.88 (d, 1H), 6.19 (t, 1H), 7.38 (d, 2H), 7.58 (d, 2H), 8.03 (s, 1H), 8.80 (d, 1H); m/z (CI) 374 [M+H].

Workup

  1. concentrationcontents are concentrated under vacuum
  2. concentrationToluene addition/concentration
  3. waitcontents are placed under high vacuum for 5 minutes
  4. additionMethanol (25 mL) is added to the reaction flask
  5. temperaturethe solution is cooled in an ice bath
  6. additionHCl in methanol (4 mL of 1.25 mL solution) is added
  7. temperatureto warm to room temperature
  8. stirringwhile stirring
  9. waitAfter 2 hours
  10. concentrationthe reaction is concentrated under vacuum to ˜3 mL of solvent
  11. waitleft
  12. custompurified directly
  13. washeluting from 95:5 water/acetonitrile/0.1% trifluoroacetic acid to 95:5 acetonitrile/water/0.1% trifluoroacetic acid
  14. concentrationThe purified fractions are concentrated under vacuum
  15. customto remove acetonitrile
  16. additionThe aqueous phase is diluted with saturated NaHCO3 (100 mL)
  17. extractionextracted with ethylacetate (2×100 mL)
  18. dry with materialThe combined organic phase is dried (Na2SO4)
  19. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-367c2e976f5e45a191da1d6e8fe9a9a3
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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