Trifluoromethanesulfonic anhydride → N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

HRID 2045844Notes

Reaction equation

HRID 2045844 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@@:8]1([NH:19][C:20]([NH:22][C:23](=[O:30])[C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[S:21])[C@H:12]([CH2:13]O)[C@@H:11]([C:15]([F:18])([F:17])[F:16])[O:10][CH2:9]1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>N1C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:9][O:10][C@H:11]([C:15]([F:16])([F:17])[F:18])[C@H:12]1[CH2:13][S:21][C:20]([NH:22][C:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[N:19]2

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydrideHCID 60169627N-(((3S,4R,5S)-3-(2-fluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

Product 1

HCID 60168236N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamideYield 62%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-20 °C

Procedure

N-(((3S,4R,5S)-3-(2-Fluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide (31.1 g) was dissolved in pyridine (150 mL), and the mixture cooled to −20° C. Trifluoromethanesulfonic anhydride (14.0 mL) was added dropwise over 30 min and the reaction was allowed to warm to 0° C. After stirring for 2 h, the reaction was quenched by the addition of ammonium chloride (sat., aq., 400 mL) and extracted with EtOAc (3×500 mL). The combined organic extracts were dried over MgSO4, concentrated in vacuo and purified by silica gel column chromatography (2% to 30% EtOAc/hex) to obtain the title compound (18.50 g). 1H NMR (400 MHz, CDCl3) δ ppm 2.86 (dd, J=13.9, 3.5 Hz, 1H), 3.25 (d, J=13.6 Hz, 1H), 3.61 (br. s., 1H), 4.00-4.10 (m, 1H), 4.66 (d, J=8.8 Hz, 1H), 4.78-4.87 (m, 1H), 7.12-7.60 (m, 6H), 7.68-7.73 (m, 1H), 7.99-8.16 (br. s., 2H), 8.62-8.66 (m, 1H)

Workup

  1. temperatureto warm to 0° C
  2. customthe reaction was quenched by the addition of ammonium chloride (sat., aq., 400 mL)
  3. extractionextracted 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 (2% to 30% EtOAc/hex)

Sources & evidence

ORD record
ord-68a56a74302c4673af5d40fa3e5473a5
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

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