Trifluoroacetic acid → HCID 86695404, compound

HRID 1487452Notes

Reaction equation

HRID 1487452 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:14]2[CH:19]=[CH:18][C:17]([C@H:20]3[O:24]C(C)(C)[N:22]([C:27](OC(C)(C)C)=[O:28])[C@@H:21]3[CH2:34][F:35])=[CH:16][CH:15]=2)[CH:5]=[N:6][C:7]=1[CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11].FC(F)(F)C(O)=O.C(N(C(C)C)CC)(C)C.[Cl:52][CH:53]([Cl:58])C(OC)=O>C(Cl)Cl.C1(C)C=CC=CC=1>[Cl:52][CH:53]([Cl:58])[C:27]([NH:22][C@H:21]([CH2:34][F:35])[C@@H:20]([C:17]1[CH:18]=[CH:19][C:14]([C:4]2[CH:5]=[N:6][C:7]([CH2:8][NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[C:2]([F:1])[CH:3]=2)=[CH:15][CH:16]=1)[OH:24])=[O:28]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8315Methyl dichloroacetateHCID 81531DiisopropylethylamineHCID 86695405HCID 86695405, compound

Product 1

HCID 86695404HCID 86695404, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

(4S,5R)-tert-butyl 5-(4-(5-fluoro-6-(methylsulfonamidomethyl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate (890 mg, 1.74 mmol) is dissolved in CH2Cl2 (20 mL), cooled to 5° C., and treated with trifluoroacetic acid (4 mL), stirred for 1 h at room temperature, diluted with toluene, concentrated to an oil. The oil is basified with aqueous sodium bicarbonate, extracted with ethyl acetate, dried, filtered, concentrated to an oil. The oil is dissolved in methanol (8 mL) and treated with diisopropylethyl amine (0.455 mL, 2.6 mmol) and methyl dichloroacetate (305 mg, 2.1 mmol), stirred at 60° C. for 18 hours, then cooled, and chromatographed on silica eluting with ethyl acetate in heptane to give the title compound. 1H NMR (400 MHz, DMSO-d6) 2.94 (s, 3H), 4.15-4.45 (m, 4H), 4.55-4.75 (m, 1H), 4.92 (t, 1H, J=3.54 Hz), 6.01 (d, 1H, J=4.29 Hz), 6.52 (s, 1H), 7.49 (d, 2H, J=8.08 Hz), 7.59 (t, 1H, J=5.94 Hz), 7.77 (d, 2H, J=8.34 Hz), 8.07 (m, 1H), 8.63 (d, 2H, J=8.84 Hz), 8.77 (s, 1H). m/z (CI) M+H 465.

Workup

  1. concentrationconcentrated to an oil
  2. extractionextracted with ethyl acetate
  3. customdried
  4. filtrationfiltered
  5. concentrationconcentrated to an oil
  6. dissolutionThe oil is dissolved in methanol (8 mL)
  7. stirringstirred at 60° C. for 18 hours
  8. temperaturecooled
  9. customchromatographed on silica eluting with ethyl acetate in heptane

Sources & evidence

ORD record
ord-c1ad2d2865ac416b9b4cfd48210dd5ed
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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