Nitric Acid → HCID 68173882, compound

HRID 707696Notes

Reaction equation

HRID 707696 reaction equation
[F:1][CH2:2][C@@H:3]1[C@@H:11]2[C@@:6]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])([N:7]=[C:8]([NH2:12])[S:9][CH2:10]2)[CH2:5][O:4]1.S(=O)(=O)(O)O.[N+:25]([O-])([OH:27])=[O:26].[OH-].[Na+]>C(O)(C(F)(F)F)=O.C(Cl)(Cl)Cl>[F:19][C:14]1[CH:15]=[CH:16][C:17]([N+:25]([O-:27])=[O:26])=[CH:18][C:13]=1[C@:6]12[CH2:5][O:4][C@H:3]([CH2:2][F:1])[C@H:11]1[CH2:10][S:9][C:8]([NH2:12])=[N:7]2

Participants

7

Reactant 4

HCID 944Nitric AcidHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 57827512HCID 57827512, compound

Product 1

HCID 68173882HCID 68173882, compoundYield 98.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

(4aS,5S,7aS)-5-(fluoromethyl)-7a-(2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine (45.85 g, 161.26 mmol) was dissolved in TFA (192 mL), and the solution was cooled to 0° C. Sulfuric acid (conc., 33.65 mL, 161.26 mmol) was added, followed by fuming nitric acid (7.78 mL, 185.44 mmol) dropwise over 25 mins. After stirring at 0° C. for 30 mins, the reaction mixture was poured onto ice (500 g)/CHCl3 (500 mL) and basified to pH 12 with 6N NaOH (aq.). The two layers were separated and the aqueous layer was extracted with CHCl3 (2×500 mL). The combined organic extracts were dried over MgSO4 and concentrated to give the product as a light orange foam (52.11 g, 98%). 1H NMR (400 MHz, CDCl3) δ ppm 2.80 (dd, J=13.26, 3.92 Hz, 1H) 3.03 (dt, J=7.77, 3.82 Hz, 1H) 3.08 (dd, J=13.39, 3.28 Hz, 1H) 3.85 (dd, J=8.84, 2.27 Hz, 1H) 4.49-4.67 (m, 4H) 7.22 (dd, J=10.99, 8.97 Hz, 1H) 8.16-8.23 (m, 1H) 8.43 (dd, J=6.82, 2.78 Hz, 1H).

Workup

  1. customThe two layers were separated
  2. extractionthe aqueous layer was extracted with CHCl3 (2×500 mL)
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-a499a2c6c47e41f794f0e58749262d37
Source dataset
uspto-grants-2015_11
Patent number
US09175013B2

Reaction notes

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