Hydrochloric Acid → [5-Fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester

HRID 457953Notes

Reaction equation

HRID 457953 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][C:5]([C:6]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=2)=[O:7])=[C:4]([OH:21])[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br[CH2:29][C:30]([O:32][CH2:33][CH3:34])=[O:31].Cl>CC(C)=O.C(OCC)(=O)C>[CH2:33]([O:32][C:30](=[O:31])[CH2:29][O:21][C:4]1[CH:3]=[C:2]([F:1])[CH:20]=[CH:19][C:5]=1[C:6](=[O:7])[NH:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=1)[CH3:34]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 184681804-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide

Product 1

HCID 22093485[5-Fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl esterYield 165%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide (5.00 g, 17.2 mmol) in acetone (86.0 mL) was treated with aq 2 N K2CO3 (13.0 mL, 25.8 mmol) and ethyl bromoacetate (1.50 mL, 9.66 mmol) and heated to 50° C. for 2 h. The solution was cooled to 0° C. and acidified to pH of 1 with 2 N HCl. The solution was diluted with ethyl acetate and washed with saturated aq NaCl. The organic layer was dried over MgSO4, filtered and concentrated. Purification by MPLC(10–100% ethyl acetate in heptane, 23 mL/min, 75 min) to give [5-fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester as a pale yellow solid (6 g, 93%): mp 78–80° C.; Rf 0.26 (40% ethyl acetate in heptane); 1H NMR (DMSO-d6 300 MHz) δ 9.01 (t, J=6 Hz, 1 H), 8.19 (t, J=1.8 Hz, 1 H), 8.10 (dd, J1=8.1 Hz, J2=1.5 Hz, 1 H), 7.89 (dd, J1=8.7 Hz, J2=6.9 Hz, 1 H), 7.79 (d, J=7.5 Hz, 1 H), 7.61 (t, J=8.1 Hz, 1 H), 7.11 (dd, J, =11.1 Hz, J2=2.4 Hz, 1 H), 6.92 (dt, J1=8.4 Hz, J2=2.4 Hz, 1 H), 5.0 (9, 2 H), 4.63 (d, J=6.3 Hz, 2 H), 4.15 (q, J=7.2 Hz, 2 H) 1.17 (t, J=6.5 Hz, 3 H). ESI-LC/MS m/z calcd for C18H17FN2O6: 376.4. Found 377.0 (M+1)+. Anal. calcd for C18H17FN2O6: C, 57.45; H, 4.55; N, 7.44. Found: C, 57.47; H, 4.64; N, 7.28.

Workup

  1. temperatureThe solution was cooled to 0° C.
  2. washwashed with saturated aq NaCl
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by MPLC(10–100% ethyl acetate in heptane, 23 mL/min, 75 min)

Sources & evidence

ORD record
ord-143e854fe000461ab3dd05ce7a828ee9
Source dataset
uspto-grants-2007_03
Patent number
US07189749B2

Reaction notes

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