Hydrochloric Acid → 6-Trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid

HRID 1697455Notes

Reaction equation

HRID 1697455 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][NH:10][C:9]2[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:8]=2[O:7]1)=[O:5])C.[OH-].[Na+].ClC(OCC1C=CC=CC=1)=O.Cl>O1CCOCC1.O>[F:19][C:16]([F:17])([F:18])[C:13]1[CH:14]=[CH:15][C:8]2[O:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][NH:10][C:9]=2[CH:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 11747775ethyl 6-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate

Product 1

HCID 203952756-Trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acidYield 66.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

6-Trifluoromethyl-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester (500 mg, 2 mmol) was dissolved in 1,4-dioxane (20 mL). Sodium hydroxide (109 mg, 2.7 mmol) was added, followed by benzyl chloroformate (311 μL, 2.2 mmol), and the reaction stirred overnight at room temperature. The reaction mixture was acidified with 2N HCl and diluted with water (20 mL), then extracted with EtOAc (3×30 mL). The combined organics were washed with brine (2×40 mL), dried (MgSO4), filtered and concentrated. Trituration using DCM/hexanes gave the title compound (330 mg, 10%) as a pale brown solid. m/z=245.7 (M−1), r.t.=2.78 mins. 1H NMR (400 MHz; CDCl3) δ 7.01 (2H, s), 6.86 (1H, s), 4.94 (1H, t), 3.66 (2H, dd).

Workup

  1. extractionextracted with EtOAc (3×30 mL)
  2. washThe combined organics were washed with brine (2×40 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d7c2fc7dd43a4f0a9cbda37a77f43de0
Source dataset
uspto-grants-2012_04
Patent number
US08163901B2

Reaction notes

Loading…