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

HRID 707683Notes

Reaction equation

HRID 707683 reaction equation
[F:1][C:2]1C(F)=[CH:6][CH:5]=[CH:4][C:3]=1[C@@:9]1([NH:37][C:38]([NH:40][C:41](=[O:48])[C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)=[S:39])[C@H:13]([CH2:14]O)[C@@H:12]([CH2:16][O:17][C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[O:11][CH2:10]1.N1C=CC=CC=1.F[C:56]([F:69])(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl>[F:1][C:2]1[C:56]([F:69])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:10][O:11][C@H:12]([CH2:16][O:17][C:18]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C@H:13]1[CH2:14][S:39][C:38]([NH:40][C:41](=[O:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)=[N:37]2

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 60169626N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide

Product 1

HCID 60168235N-((4aS,5S,7aS)-7a-(2,3-difluorophenyl)-5-((trityloxy)methyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide, obtained in Preparation Example 1-(4), (19.06 g) was dissolved in DCM (75 mL). Pyridine (8.6 mL) was added, and the mixture cooled to 0° C. Trifluoromethanesulfonic anhydride (9.6 mL) was added dropwise and the reaction was allowed to stir at 0° C. After 90 min, the reaction was quenched by the careful addition of NaHCO3 (sat., aq., 250 mL) and extracted with EtOAc (3×250 mL). The combined organic extracts were dried over MgSO4, concentrated in vacuo and purified by silica gel column chromatography (0% to 30% EtOAc/hex) to obtain the title compound (14.52 g). 1H NMR (400 MHz, CDCl3) δ ppm 2.63-2.76 (m, 1H), 3.07-3.24 (m, 2H), 3.32-3.52 (m, 3H), 3.99-4.11 (m, 1H), 4.53-4.63 (m, 2H), 7.09-7.56 (m, 21H), 8.08-8.30 (m, 2H)

Workup

  1. customthe reaction was quenched by the careful addition of NaHCO3 (sat., aq., 250 mL)
  2. extractionextracted with EtOAc (3×250 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. custompurified by silica gel column chromatography (0% to 30% EtOAc/hex)

Sources & evidence

ORD record
ord-6b0be856cae643e5b3c7079403397bf5
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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