Pyridine → HCID 57827501, compound

HRID 707694Notes

Reaction equation

HRID 707694 reaction equation
[F:1][CH2:2][C@H:3]1[O:7][CH2:6][C@@:5]([NH:15][C:16]([NH:18][C:19](=[O:26])[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[S:17])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[C@@H:4]1[CH2:27]O.N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>>[F:1][CH2:2][C@@H:3]1[C@@H:4]2[C@@:5]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[F:14])([N:15]=[C:16]([NH:18][C:19](=[O:26])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[S:17][CH2:27]2)[CH2:6][O:7]1

Participants

4

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 86724403HCID 86724403, compound

Product 1

HCID 57827501HCID 57827501, compoundYield 94.2%

Conditions

Temperature
0 °C

Procedure

N-(((3S,4R,5S)-5-(fluoromethyl)-3-(2-fluorophenyl)-4-(hydroxymethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide (78.70 g, 193.63 mmol) was dissolved in pyridine (391 mL, 5190.48 mmol), and the mixture cooled to 0° C. Trifluoromethanesulfonic anhydride (43.98 mL, 261.40 mmol) was added dropwise over 40 min (internal temperature increased from 4° C. to 18° C.). The reaction was stirred in an ice bath for 1 h and 25 mins. It was quenched by the slow addition of ammonium chloride (sat., aq., 260 mL) and then water (390 mL). The aqueous layer was extracted with EtOAc (3×500 mL). The combined organic extracts were dried over MgSO4, concentrated in vacuo and purified by silica gel column chromatography (20% to 60% EtOAc/hex) to obtain the title compound (70.86 g, 94%). 1H NMR (400 MHz, CDCl3) δ ppm 2.83 (dd, J=13.64, 3.79 Hz, 1H) 3.30 (dd, J=13.89, 3.54 Hz, 1H) 3.38-3.47 (m, 1H) 4.07 (dd, J=9.22, 2.65 Hz, 1H) 4.51-4.78 (m, 4H) 7.15 (ddd, J=12.44, 8.15, 1.14 Hz, 1H) 7.22 (td, J=7.58, 1.26 Hz, 1H) 7.34-7.41 (m, 1H) 7.41-7.48 (m, 3H) 7.49-7.56 (m, 1H) 8.10-8.18 (m, 2H).

Workup

  1. temperature(internal temperature increased from 4° C. to 18° C.)
  2. customIt was quenched by the slow addition of ammonium chloride (sat., aq., 260 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (3×500 mL)
  4. dry with materialThe combined organic extracts were dried over MgSO4
  5. concentrationconcentrated in vacuo
  6. custompurified by silica gel column chromatography (20% to 60% EtOAc/hex)

Sources & evidence

ORD record
ord-a61c599cacdc4840b72bd45ea6478769
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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