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

HRID 1429620Notes

Reaction equation

HRID 1429620 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@:9]1([NH:20][C:21]([NH:23][C:24](=[O:31])[C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[S:22])[C@H:13]([CH2:14]O)[C@@H:12]([C:16]([F:19])([F:18])[F:17])[O:11][CH2:10]1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>N1C=CC=CC=1>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:10][O:11][C@H:12]([C:16]([F:18])([F:17])[F:19])[C@H:13]1[CH2:14][S:22][C:21]([NH:23][C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[N:20]2

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydride2×HCID 86668364N-(((3 S,4R,5 S)-3-(2,3-Difluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

Product 1

HCID 70496055N-((4aS,5S,7aS)-7a-(2,3-difluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamideYield 41.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-20 °C

Procedure

N-(((3 S,4R,5 S)-3-(2,3-Difluorophenyl)-4-(hydroxymethyl)-5-(trifluoromethyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide (2.99 g) was dissolved in pyridine (14 mL), and the mixture cooled to −20° C. Trifluoromethanesulfonic anhydride (1.55 mL) was added dropwise over 10 min and the reaction mixture was allowed to warm to −10° C. After stirring for 2 h, a further portion of trifluoromethanesulfonic anhydride (1.0 mL) was added dropwise over 10 min, the reaction was stirred for a further 2 h, and was then quenched by the addition of ammonium chloride (sat., aq., 50 mL) and extracted with EtOAc (3×100 mL). The combined organic extracts were dried over MgSO4, concentrated in vacuo and purified by silica gel column chromatography (5% to 20% EtOAc/hex) to obtain the title compound (1.20 g). 1H NMR (400 MHz, CDCl3) δ ppm 2.86 (d, J=10.6 Hz, 1 H), 3.20 (br. s., 1 H), 3.55 (br. s., 1 H), 4.04 (br. s., 1 H), 4.65 (d, J=8.8 Hz, 1 H), 4.81 (br. s., 1 H), 7.06-7.24 (m, 3 H), 7.40-7.64 (m, 3 H), 7.82-8.21 (m, 2 H)

Workup

  1. temperatureto warm to −10° C
  2. stirringthe reaction was stirred for a further 2 h
  3. customwas then quenched by the addition of ammonium chloride (sat., aq., 50 mL)
  4. extractionextracted with EtOAc (3×100 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by silica gel column chromatography (5% to 20% EtOAc/hex)

Sources & evidence

ORD record
ord-a4c2380f9abf4cacaff6107fcfee7ca2
Source dataset
uspto-grants-2015_01
Patent number
US08940734B2

Reaction notes

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