Tetrahydrofuran → Methyl 4-fluoro-3-{[(2-propen-1-yloxy)carbonyl]amino}benzoate

HRID 239277Notes

Reaction equation

HRID 239277 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[F:12])[C:5]([O:7][CH3:8])=[O:6].[C:13]([O-:16])(O)=[O:14].[Na+].[CH2:18]1[CH2:22]OC[CH2:19]1>>[F:12][C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[NH:1][C:13]([O:16][CH2:22][CH:18]=[CH2:19])=[O:14]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 12541234Methyl 3-amino-4-fluorobenzoate

Product 1

HCID 57989714Methyl 4-fluoro-3-{[(2-propen-1-yloxy)carbonyl]amino}benzoateYield 98%

Procedure

To a solution of methyl 3-amino-4-fluorobenzoate (109 g, 644 mmol) in THF (2000 mL), saturated NaHCO3 (68 g, 805 mmol) was added. Then 2-propen-1-yl chloridocarbonate (93 g, 773 mmol) was added dropwise at 0° C. The mixture was stirred at rt for 2 h. The solution was extracted with EtOAc (500 mL×3). The combined organic layers were washed with water and brine successively, dried over Na2SO4, filtered and concentrated under reduced pressure to give the crude product (160 g, 98%), which was used in the next step directly. 1H NMR (400 MHz, CDCl3) δ ppm 8.72-8.81 (m, 1H), 7.71-7.79 (m, 1H), 7.09-7.16 (m, 1H), 6.87-6.94 (br, 1H), 5.91-6.03 (m, 1H), 5.41 (d, J=17.1 Hz, 1H), 5.28 (d, J=10.5, 1H), 4.70 (d, J=10.5 Hz, 1H), 4.70 (d, J=5.5 Hz, 2H), 3.90 (s, 3H).

Workup

  1. additionThen 2-propen-1-yl chloridocarbonate (93 g, 773 mmol) was added dropwise at 0° C
  2. extractionThe solution was extracted with EtOAc (500 mL×3)
  3. washThe combined organic layers were washed with water and brine successively
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e64054a119b6471fb61b9142c152c2ae
Source dataset
uspto-grants-2014_02
Patent number
US08642759B2

Reaction notes

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