Trifluoromethanesulfonic anhydride → N-((4aS*,5R*,7aS*)-7a-(2,4-Difluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

HRID 68384Notes

Reaction equation

HRID 68384 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@@:9]1([NH:17][C:18]([NH:20][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[S:19])[C@H:13]([CH2:14]O)[C@@H:12]([CH3:16])[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[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:10][O:11][C@H:12]([CH3:16])[C@H:13]1[CH2:14][S:19][C:18]([NH:20][C:21](=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[N:17]2

Participants

4

Reactant 2

HCID 67749Trifluoromethanesulfonic anhydride2×HCID 86707822N-(((3S*,4R*,5R*)-3-(2,4-Difluorophenyl)-4-(hydroxymethyl)-5-methyltetrahydrofuran-3-yl)carbamothioyl)benzamide

Product 1

HCID 86707823N-((4aS*,5R*,7aS*)-7a-(2,4-Difluorophenyl)-5-methyl-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
-20 °C

Procedure

N-(((3S*,4R*,5R*)-3-(2,4-Difluorophenyl)-4-(hydroxymethyl)-5-methyltetrahydrofuran-3-yl)carbamothioyl)benzamide (165 mg, 0.41 mmol) was dissolved in pyridine (2 mL) and the solution was cooled to −20° C. Trifluoromethanesulfonic acid anhydride (68 μl, 0.41 mmol) was added dropwise into the reaction. After 45 minutes, the reaction was incomplete so a further aliquot of trifluoromethanesulfonic acid anhydride (68 μl, 0.41 mmol) was added and the reaction stirred for a further 1 hour. The reaction was quenched with saturated NaHCO3 and extracted with Et2O (×2). The combined organics were concentrated and the residue purified by column chromatography, eluting with 0-30% EtOAc in n-hexane to leave the title compound as a yellow foam. (95 mg). 1H NMR (400 MHz, CDCl3) δ ppm: 8.11-8.17 (m, 2H), 7.38-7.62 (m, 4H), 6.86-7.02 (m, 2H), 4.47-4.58 (m, 2H), 4.01 (dd, J=2.63, 9.48 Hz, 1H), 3.17-3.26 (m, 1H), 2.75-2.86 (m, 2H), 1.42 (d, J=6.11 Hz, 3H).

Workup

  1. additionwas added
  2. customThe reaction was quenched with saturated NaHCO3
  3. extractionextracted with Et2O (×2)
  4. concentrationThe combined organics were concentrated
  5. customthe residue purified by column chromatography
  6. washeluting with 0-30% EtOAc in n-hexane

Sources & evidence

ORD record
ord-745d6ebdd654484783a6d59ea6dad823
Source dataset
uspto-grants-2014_09
Patent number
US08822455B2

Reaction notes

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