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 707705Notes

Reaction equation

HRID 707705 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.[NH4+].[Cl-]>C(Cl)Cl.O>[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

7

Reactant 4

HCID 1049PyridineHCID 25517Ammonium ChlorideHCID 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)benzamideYield 101.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a solution of N-(((3S,4R,5S)-3-(2,3-difluorophenyl)-4-(hydroxymethyl)-5-((trityloxy)methyl)tetrahydrofuran-3-yl)carbamothioyl)benzamide (34.0 g, 0.0511 mol, 1.0 equiv.) in CH2Cl2 (204 mL) at −20° C., pyridine (10.3 ml, 0.128 mol, 2.50 equiv.) was added. A solution of trifluoromethanesulfonic anhydride (9.46 mL, 0.0563 mol, 1.10 equiv.) in CH2Cl2 (34 mL) was then added over 12 min while maintaining temperature below −17° C. The reaction was stirred for 30 min at −20° C. then allowed to warm up slowly to 5° C. Sat aq. NH4Cl (85 mL) and water (32 mL) were added. The aqueous layer was then extracted with CH2Cl2 (68 mL). The organic phase was concentrated under reduced pressure providing title compound (33.6 g) as an orange foam.

Workup

  1. temperaturewhile maintaining temperature below −17° C
  2. temperatureto warm up slowly to 5° C
  3. extractionThe aqueous layer was then extracted with CH2Cl2 (68 mL)
  4. concentrationThe organic phase was concentrated under reduced pressure

Sources & evidence

ORD record
ord-96971bfea9d34b16a5c8491329daa04c
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

Loading…