Hydrochloric Acid → Methyl 3-propyl-1,2-benzisoxazole-5-carboxylate

HRID 349040Notes

Reaction equation

HRID 349040 reaction equation
O[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1/[C:12](=[N:16]/[OH:17])/[CH2:13][CH2:14][CH3:15].S(Cl)(Cl)=O.N1C=CC=CC=1.Cl>C(OCC)C>[CH2:13]([C:12]1[C:3]2[CH:4]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:10]=[CH:11][C:2]=2[O:17][N:16]=1)[CH2:14][CH3:15]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 24386Thionyl ChlorideHCID 136200566methyl 4-hydroxy-3-[(E)-N-hydroxy-C-propylcarbonimidoyl]benzoate

Product 1

HCID 21086192Methyl 3-propyl-1,2-benzisoxazole-5-carboxylateYield 58.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To an ice-cold stirred solution of methyl 4-hydroxy-3-[(1E)-N-hydroxybutanimidoyl]benzoate (170 mg, 0.7 mmol) in diethyl ether (5 mL) was added a mixture of thionyl chloride (60 μL, 0.8 mmol) and pyridine (580 μL, 7.2 mmol) in diethyl ether (5 mL). After 2.5 h the mixture was poured over ice-water and acidified to pH=1 with 1 N hydrochloric acid. The mixture was then partitioned between water and ethyl acetate. The organic layer was washed with saturated sodium bicarbonate, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, 10:1 hexanes/ethyl acetate) provided methyl 3-propyl-1,2-benzisoxazole-5-carboxylate (90 mg): 1H NMR (300 MHz, CDCl3): δ 8.36–8.35 (m, 1H), 8.07–8.04 (m, 1H), 7.52–7.49 (m, 1H), 3.95 (s, 3H), 2.96–2.91 (m, 2H), 2.00–1.87 (m, 2H), 1.09–1.04 (m, 3H).

Workup

  1. customThe mixture was then partitioned between water and ethyl acetate
  2. washThe organic layer was washed with saturated sodium bicarbonate
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto afford a crude oil
  7. customPurification by flash column chromatography (silica, 10:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-795b08ebbdad4cc2ad62eb9cecfa3053
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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