Triethylamine → 4,4-Dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazoline

HRID 840349Notes

Reaction equation

HRID 840349 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[C:9](=[O:10])[O:8][CH2:7]2)([OH:3])=O.ClC(OCC)=O.C(N(CC)CC)C.[NH2:27][C:28]([CH3:32])([CH3:31])[CH2:29]O.S(Cl)(Cl)=O>CC(C)=O.O>[CH3:29][C:28]1([CH3:32])[CH2:31][O:3][C:1]([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[C:9](=[O:10])[O:8][CH2:7]3)=[N:27]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 118072-Amino-2-methyl-1-propanolHCID 24386Thionyl ChlorideHCID 785171,3-Dihydro-1-oxoisobenzofuran-5-carboxylic acid

Product 1

HCID 113221954,4-Dimethyl-2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)oxazolineYield 66.8%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolvent3×HCID 962WaterSolvent

Conditions

Temperature
-10 °C

Procedure

Acetone (40 ml) is stirred and 5-carboxyphthalide (2 g ,0.01 1 mol) are added at about 20° C. The mixture is cooled to −10° C. and ethyl chloroformate (1.18 ml, 0.012 mol) is added. At the end of the addition, a solution of triethylamine (1.56 ml ,0.011 mol) in acetone (3.50 ml) is added keeping the temperature of the mixture at or below −10° C. The temperature of the mixture is allowed to rise to 10-13° C. and, after 30 minutes, it is brought to −10° C. and a solution of 2-amino-2-methyl-1-propanol (3.0 g ,0.034 mol) in acetone (5 ml) is quickly added to the mixture. The temperature is allowed to rise to 15-20° C., whereby the reaction is completed as it may be verified by HPLC. To the mixture thus obtained, cooled to −5° C., thionyl chloride (2.5 ml, 0.034 mol) is added, the temperature is allowed to rise to about 20° C. and after 30 minutes the ring closure is completed. The reaction mixture is concentrated in vacuo leaving a residue, which is treated with water (20 ml). The mixture is concentrated again and a further amount of water (10 ml) is added to the residue, the pH is made basic by addition of 25% ammonia and the mixture is cooled to 5° C. The product is filtered off, washed with water and dried in vacuo. Yield: 1.70 g. Total yield: 66.8%.

Workup

  1. additionAt the end of the addition
  2. custombelow −10° C
  3. customis brought to −10° C.
  4. customto rise to 15-20° C.
  5. customTo the mixture thus obtained
  6. temperaturecooled to −5° C.
  7. waitto rise to about 20° C. and after 30 minutes
  8. concentrationThe reaction mixture is concentrated in vacuo
  9. customleaving a residue, which
  10. concentrationThe mixture is concentrated again
  11. additiona further amount of water (10 ml) is added to the residue
  12. additionthe pH is made basic by addition of 25% ammonia
  13. temperaturethe mixture is cooled to 5° C
  14. filtrationThe product is filtered off
  15. washwashed with water
  16. customdried in vacuo

Sources & evidence

ORD record
ord-4d35e8adce2543fbb18ce437cfb85784
Source dataset
uspto-grants-2002_04
Patent number
US06365747B1

Reaction notes

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