2-[[(1-Oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl]amino]-2-methyl-1-propanol → 4,4-Dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline

HRID 1072765Notes

Reaction equation

HRID 1072765 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([NH:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:16])=O)=[CH:8][CH:9]=2)[CH2:4][O:3]1>S(Cl)(Cl)=O>[CH3:17][C:14]1([CH3:18])[CH2:15][O:16][C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[C:2](=[O:1])[O:3][CH2:4]3)=[N:13]1

Participants

3

Reactant 1

HCID 111960052-[[(1-Oxo-1,3-dihydroisobenzofuran-5-yl)carbonyl]amino]-2-methyl-1-propanol

Product 1

HCID 113221954,4-Dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
-5 °C

Procedure

To thionyl chloride (130 ml), cooled at −10° C., 2-[[(1-oxo-1,3-dihydroiso-benzofuran-5-yl)carbonyl]amino]-2-methyl-1-propanol (85 g, 0.34 mol) is added portionwise with stirring. The temperature is maintained at −10→−5° C. for 1.5 hours whereafter the cooling is removed and the reaction is stirred overnight at ambient temperature. It is then cooled to 0° C. and tetrahydrofuran (860 mL) is added dropwise keeping the temperature below +8° C. The obtained suspension is kept under stirring for 2 hours at 5° C., and then filtered and the crystals washed with tetrahydrofuran (150 mL). The wet solid is dissolved in deionized water (400 mL) and the pH is adjusted to 9.1 by the addition of 25% aqueous ammonia. The solid is filtered, washed with deionized water and dried for 14 hours at 50° C. under reduced pressure. Yield: 62.8 g (80%) of a white product having a purity (HPLC, peak area)=94%. 1H NMR (DMSO d-6, 500 MHz): 1.31 (6H, s), 4.18 (2H, s), 5.44 (2H, s), 7.9 (1H, d, J=11.3 Hz), 8.01 (1H, d, J=11.3 Hz), 8.12 (1H, s).

Workup

  1. customis removed
  2. stirringthe reaction is stirred overnight at ambient temperature
  3. temperatureIt is then cooled to 0° C.
  4. additiontetrahydrofuran (860 mL) is added dropwise
  5. customthe temperature below +8° C
  6. stirringunder stirring for 2 hours at 5° C.
  7. filtrationfiltered
  8. washthe crystals washed with tetrahydrofuran (150 mL)
  9. dissolutionThe wet solid is dissolved in deionized water (400 mL)
  10. additionthe pH is adjusted to 9.1 by the addition of 25% aqueous ammonia
  11. filtrationThe solid is filtered
  12. washwashed with deionized water
  13. customdried for 14 hours at 50° C. under reduced pressure

Sources & evidence

ORD record
ord-70c7ed47736f46989190b812793cc1c7
Source dataset
uspto-grants-2005_06
Patent number
US06911548B2

Reaction notes

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