Sodium Iodide → HCID 59394948, compound

HRID 471896Notes

Reaction equation

HRID 471896 reaction equation
[F:1][C:2]([F:20])([F:19])[O:3][C:4]1[CH:5]=[CH:6][C:7]2[O:12][CH:11]([C:13]([O:15]CC)=[O:14])[CH2:10][NH:9][C:8]=2[CH:18]=1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+].Br[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1>CN(C=O)C>[CH3:38][O:37][C:34]1[CH:35]=[CH:36][C:31]([CH2:30][N:9]2[CH2:10][CH:11]([C:13]([OH:15])=[O:14])[O:12][C:7]3[CH:6]=[CH:5][C:4]([O:3][C:2]([F:1])([F:19])[F:20])=[CH:18][C:8]2=3)=[CH:32][CH:33]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 1650214-Methoxybenzyl bromideHCID 59394938HCID 59394938, compound

Product 1

HCID 59394948HCID 59394948, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Ethyl 6-(trifluoromethoxy)-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate (775 mg, 2.66 mmol) was dissolved in DMF (4 mL) containing K2CO3 (1103 mg, 7.98 mmol), sodium iodide (80 mg, 0.53 mmol). 1-(Bromomethyl)-4-methoxy-benzene (1070 mg, 776 μL, 5.32 mmol) was added slowly to the above reaction mixture. The mixture was heated at 60° C. for 6 h. After evaporation of the solvent, the residue was treated with water and extracted with dichloromethane. The organic extracts were dried over Na2SO4 and evaporated in vacuo. The residue was chromatographed over a silica gel column (0-25% ethyl acetate/hexanes) to provide 4-(4-methoxybenzyl)-6-(trifluoromethoxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine-2-carboxylic acid (639 mg, 1.553 mmol, 58.37%) as a white solid. LC/MS m/z 412.4 [M+H]+. 1H NMR (400.0 MHz, DMSO-d6) δ 7.18 (d, J=8.5 Hz, 2H), 6.88 (d, J=8.6, 2H), 6.86 (d, J=8.6 Hz, 1H), 6.68 (d, J=2.1 Hz, 1H), 6.54 (d, J=8.7 Hz, 1H), 5.09 (t, J=3.3 Hz, 1H), 4.45 (d, J=15.4 Hz, 1H), 4.29 (d, J=15.3 Hz, 1H), 4.16-4.05 (m, 2H), 3.73 (s, 3H), 3.52-3.42 (m, 2H), 1.13 (t, J=7.1 Hz, 3H).

Workup

  1. customAfter evaporation of the solvent
  2. additionthe residue was treated with water
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic extracts were dried over Na2SO4
  5. customevaporated in vacuo
  6. customThe residue was chromatographed over a silica gel column (0-25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d8382f9a22bf43f1aa402e1bc178238e
Source dataset
uspto-grants-2014_01
Patent number
US08633189B2

Reaction notes

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