Toluene → 3-[2-(3-Chlorophenyl)ethyl]-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-pyridine

HRID 270663

Reaction equation

HRID 270663 reaction equation
C1C[O:4][CH2:3]C1.[Li+].C[CH:8]([N-:10][CH:11]([CH3:13])[CH3:12])[CH3:9].O1[CH2:18][CH2:17][N:16]=C1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23]Cl.[C:28]1([CH3:34])C=CC=C[CH:29]=1>O>[Cl:19][C:20]1[CH:21]=[C:22]([CH2:23][CH2:34][C:28]2[C:9]([C:8]3[O:4][CH2:3][C:11]([CH3:12])([CH3:13])[N:10]=3)=[N:16][CH:17]=[CH:18][CH:29]=2)[CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 5

HCID 1140TolueneHCID 8028Tetrahydrofuran2×HCID 12103m,alpha-DichlorotolueneHCID 68157OxazolineHCID 2724682Lithium diisopropylamide

Product 1

HCID 102677853-[2-(3-Chlorophenyl)ethyl]-2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-pyridineYield 80.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

521.7 ml of anhydrous THF and 521.7 ml of 2M LDA solution (1.04 mol) are placed in a 3-litre jacketed reactor equipped with a mechanical stirrer and thermometer, and maintained under a nitrogen atmosphere, the internal temperature is brought to −5° C. and a solution consisting of 158.8 g of oxazoline (0.835 mol) and 834.7 ml of anhydrous THF is then added slowly, keeping the temperature at about 0° C. After adding a few drops of solution, a strong blue-violet colour is obtained. The total addition time is about one hour. 154.6 g (0.96 mol) of 3chlorobenzyl chloride are then added over about 1.5 hours, while still maintaining the temperature at 0° C. At the end of the reaction, 521.7 g of water are added while bringing the temperature to 20-25° C. The two phases are then separated and the organic phase is evaporated to give an oil. The crude product thus obtained is taken up in toluene and filtered through Tonsil. The filtrate is concentrated to give 268.1 g of an oil with an HPLC titre of 79%. 91.8% conversion, yield=80.2%

Workup

  1. customequipped with a mechanical stirrer
  2. temperaturethermometer, and maintained under a nitrogen atmosphere
  3. customis brought to −5° C.
  4. additionis then added slowly
  5. customat about 0° C
  6. customa strong blue-violet colour is obtained
  7. additionThe total addition time
  8. additionare added
  9. customto 20-25° C
  10. customThe two phases are then separated
  11. customthe organic phase is evaporated
  12. customto give an oil
  13. customThe crude product thus obtained
  14. filtrationfiltered through Tonsil
  15. concentrationThe filtrate is concentrated

Sources & evidence

ORD record
ord-2e436d3a1b6946028cfc74c1f83c2db0
Source dataset
uspto-grants-2008_11
Patent number
US07449583B2

Linked notes

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