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

HRID 14250Notes

Reaction equation

HRID 14250 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-abb27dfc3dfb48959c05bb37a30c70aa
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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