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

HRID 707684Notes

Reaction equation

HRID 707684 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([CH2:18][O:19]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C@H:14]1[CH2:13][S:12][C:11]([NH:39][C:40](=[O:47])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[N:10]2.O.Cl>CO>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]12[CH2:17][O:16][C@H:15]([CH2:18][OH:19])[C@H:14]1[CH2:13][S:12][C:11]([NH:39][C:40](=[O:47])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)=[N:10]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 962WaterHCID 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

Product 1

HCID 68173766N-((4aS,5S,7aS)-7a-(2,3-difluorophenyl)-5-(hydroxymethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

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, obtained in preparation example 1-(5), (8.42 g) was suspended in methanol (100 mL) and water (3 mL) and conc. hydrochloric acid (5 mL) were added. The reaction mixture was stirred vigorously overnight, and then concentrated under reduced pressure to a volume of about 30 mL. The mixture was then carefully neutralised with NaHCO3 (sat., aq., 100 mL) and extracted with EtOAc (3×100 mL). The combined organic portions were dried over MgSO4, evaporated, and the residue purified by silica gel column chromatography (0% to 50% EtOAc in hexanes) to afford the title compound (4.20 g). 1H NMR (400 MHz, CDCl3) δ ppm 1.94 (br. s., 1H), 2.83 (d, J=10.6 Hz, 1H), 3.14-3.49 (m, 2H), 3.77 (d, J=8.8 Hz, 1H), 3.97 (dd, J=11.7, 2.7 Hz, 1H), 4.08 (d, J=6.3 Hz, 1H), 4.46-4.63 (m, 2H), 7.07-7.25 (m, 3H), 7.37-7.60 (m, 3H), 8.00-8.26 (m, 2H)

Workup

  1. concentrationconcentrated under reduced pressure to a volume of about 30 mL
  2. extractionextracted with EtOAc (3×100 mL)
  3. dry with materialThe combined organic portions were dried over MgSO4
  4. customevaporated
  5. customthe residue purified by silica gel column chromatography (0% to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ef50229f989542f6ab8900e5b8b0d43d
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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