Nitric Acid → (4aS,5S,7aS)-7a-(2-fluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

HRID 2045845Notes

Reaction equation

HRID 2045845 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:16][O:15][C@H:14]([C:17]([F:20])([F:19])[F:18])[C@H:13]1[CH2:12][S:11][C:10]([NH:21]C(=O)C1C=CC=CC=1)=[N:9]2.S(=O)(=O)(O)O.[N+:35]([O-])([OH:37])=[O:36].[OH-].[Na+]>C(O)(C(F)(F)F)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N+:35]([O-:37])=[O:36])=[CH:4][C:3]=1[C@:8]12[CH2:16][O:15][C@H:14]([C:17]([F:20])([F:19])[F:18])[C@H:13]1[CH2:12][S:11][C:10]([NH2:21])=[N:9]2

Participants

6

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 60168236N-((4aS,5S,7aS)-7a-(2-fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Product 1

HCID 60168240(4aS,5S,7aS)-7a-(2-fluoro-5-nitrophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

N-((4aS,5S,7aS)-7a-(2-Fluorophenyl)-5-(trifluoromethyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (5.15 g) was dissolved in TFA (75 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 20 mL) was added, followed by fuming nitric acid (2 mL) dropwise over 20 mins. After stirring at 0° C. for 90 mins, the reaction mixture was poured onto ice (200 g) and basified to pH 12 with 6N NaOH (aq.). After allowing the ice to melt, the mixture was extracted with EtOAc (3×500 mL), and the combined organic portions dried over MgSO4 and evaporated to afford the title compound (22.1 g, purity approx. 71%) which was used in the subsequent step without purification. 1H NMR (400 MHz, CDCl3) δ ppm 2.89 (d, J=3.8 Hz, 1H), 3.09 (br. s., 1 H), 3.28-3.54 (m, 1H), 3.80-4.03 (m, 1H), 4.50-4.70 (m, 3H), 4.71-4.86 (m, 1H), 7.21-7.30 (m, 1H), 8.18-8.28 (m, 1H), 8.45 (dd, J=6.8, 2.8 Hz, 1H)

Workup

  1. additionthe reaction mixture was poured onto ice (200 g)
  2. extractionthe mixture was extracted with EtOAc (3×500 mL)
  3. dry with materialthe combined organic portions dried over MgSO4
  4. customevaporated

Sources & evidence

ORD record
ord-a899f1f09f2d4575a53534a3595f290f
Source dataset
uspto-grants-2013_11
Patent number
US08592408B2

Reaction notes

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