Methanol → HCID 16658841, compound

HRID 1350166Notes

Reaction equation

HRID 1350166 reaction equation
F[C:2]1[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[CH:16]=[CH:15][C:3]=1[N:4]([CH2:10][C:11]([F:14])([F:13])[F:12])[C@H:5]([CH2:8][CH3:9])[CH2:6][OH:7].[H-].[Na+].CO>C1COCC1>[CH2:8]([C@H:5]1[N:4]([CH2:10][C:11]([F:14])([F:13])[F:12])[C:3]2[CH:15]=[CH:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][C:2]=2[O:7][CH2:6]1)[CH3:9]

Participants

5

Reactant 3

HCID 887MethanolHCID 24758Sodium hydrideHCID 16659481HCID 16659481, compound

Product 1

HCID 16658841HCID 16658841, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 190 g (0.612 mole) of the crude (2R)-2-[2-fluoro-4-nitro(2,2,2-trifluoroethyl)anilino]-1-butanol in 1 Liter of dry THF was added dropwise to a stirred suspension of 36.77 g (0.919 mole, 1.5 eq) of sodium hydride in 1.5 L of dry THF under nitrogen atmosphere. After complete addition, the reaction mixture was refluxed for 3 h when TLC of the reaction mixture indicated complete conversion. After cooling to room temperature, 400 mL of methanol was added to destroy excess sodium hydride. The reaction mixture was poured into ice-cold water and extracted with ethyl acetate. The organic portions were combined, washed with brine and dried over MgSO4. After filtration, the solvents were evaporated under reduced pressure. The crude product thus obtained was purified by silica gel column chromatography (ethyl acetate:hexanes 1:9) to obtain (+)-(3R)-3-ethyl-3,4-dihydro-7-nitro-4-(2,2,2-trifluoroethyl)-2H-1,4-benzoxazine as a yellow crystalline solid. Yield 71 g (40%). [α]D=+56.6 (CHCl3, c 7.8); 1H NMR (CDCl3) δ 7.80 (1H, dd, J=2.56, 8.98), 7.71 (1H, d, J=2.57), 6.72 (1H, d, J=9.07), 4.34 (1H, dd, J=1.44, 11.02), 4.12 (1H, m), 4.06 (1H, dd, J=2.12, 11.04), 3.79 (1H, m), 3.37 (1H, m), 1.68 (2H, m), 1.00 (3H, t, J=7.54). 13C NMR: ppm 142.6, 139.1, 138.6, 126.1, 118.6, 112.6, 110.8, 64.9, 58.9, 50.6, 22.5 and 10.3.

Workup

  1. additionAfter complete addition
  2. temperaturethe reaction mixture was refluxed for 3 h when TLC of the reaction mixture
  3. customto destroy excess sodium hydride
  4. additionThe reaction mixture was poured into ice-cold water
  5. extractionextracted with ethyl acetate
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationAfter filtration
  9. customthe solvents were evaporated under reduced pressure
  10. customThe crude product thus obtained
  11. customwas purified by silica gel column chromatography (ethyl acetate:hexanes 1:9)

Sources & evidence

ORD record
ord-6174df4cd6b646f3a5c0b036681f54af
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

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