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

HRID 590118Notes

Reaction equation

HRID 590118 reaction equation
[NH2:1][C:2]1[C:3]([O:12][CH3:13])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].[C:14]([O-:17])(O)=[O:15].[Na+].[CH2:19]1[CH2:23]OC[CH2:20]1>>[CH3:13][O:12][C:3]1[C:2]([NH:1][C:14]([O:17][CH2:23][CH:19]=[CH2:20])=[O:15])=[CH:11][CH:10]=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6]

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 13338715Methyl 3-amino-2-methoxybenzoate

Product 1

HCID 57989622Methyl 2-(methyloxy)-3-{[(2-propen-1-yloxy)carbonyl]amino}benzoateYield 80%

Procedure

To a solution of methyl 3-amino-2-methoxybenzoate (94 g, 580 mmol) (from composite batches prepared as described above) in THF (1800 mL), saturated NaHCO3 (60.9 g, 725 mmol) was added. Then 2-propen-1-yl chloridocarbonate (83.7 g, 696 mmol) was added dropwise at 0° C. The mixture was stirred at rt for 2 h. The solution was extracted with EtOAc (700 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 title compound of Step D (123 g, 80% yield), which was used in the next step directly. 1H NMR (400 MHz, CDCl3) δ ppm 8.25-8.35 (m, 1H), 7.49-7.53 (m, 1H), 7.36-7.42 (br, 1H), 7.10-7.18 (m, 1H), 5.91-6.07 (m, 1H), 5.75-5.90 (m, 2H), 4.63-4.70 (m, 2H), 3.92 (s, 3H), 3.86 (s, 3H).

Workup

  1. additionThen 2-propen-1-yl chloridocarbonate (83.7 g, 696 mmol) was added dropwise at 0° C
  2. extractionThe solution was extracted with EtOAc (700 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-55599c7bd8db4719b201dd833f602082
Source dataset
uspto-grants-2016_01
Patent number
US09233956B2

Reaction notes

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