Triethylamine → 4,4-dimethyl-2-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-4,5-dihydro-1,3-oxazole

HRID 251442Notes

Reaction equation

HRID 251442 reaction equation
Cl[CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[O:13][CH2:14][C:15]([CH3:18])([CH3:17])[N:16]=2)=[CH:8][CH:7]=1.Cl.[CH3:20][C@@H:21]1[CH2:25][CH2:24][CH2:23][NH:22]1.C(N(CC)CC)C>>[CH3:17][C:15]1([CH3:18])[CH2:14][O:13][C:12]([C:9]2[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH2:3][CH2:2][N:22]3[CH2:23][CH2:24][CH2:25][C@H:21]3[CH3:20])=[CH:7][CH:8]=2)=[N:16]1

Participants

4

Reactant 3

HCID 8471Triethylamine2×HCID 11147704(2R)-(-)-2-Methylpyrrolidine hydrochlorideHCID 11950718HCID 11950718, compound

Product 1

HCID 119521504,4-dimethyl-2-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-4,5-dihydro-1,3-oxazoleYield 21%

Conditions

Temperature
120 °C

Procedure

A mixture of 2-[4-(3-chloropropoxy)phenyl]-4,4-dimethyl-4,5-dihydro-1,3-oxazole ax10 (0.25 g, 0.9 mmol, 1 eq), 0.15 g of (2R)-2-methylpyrrolidine hydrochloride (1.2 mmol, 1.4 eq) and triethylamine (0.3 ml, 2.2 mmol, 2.4 eq) is stirred under microwave irradiation (120° C., 3.75 h). The mixture is then filtered. Triethylamine (0.2 ml, 1.44 mmol, 1.6 eq) is added to the organic layer, and the mixture is again stirred under microwave irradiation, at 120° C. for another 1.5 h. The solvent is then removed under vacuum and the residue diluted with ethyl acetate. The organic layer is washed with water, with a saturated solution of sodium chloride, dried over magnesium sulfate and concentrated under vacuum. The residue is purified over silicagel (eluent: dichloromethane/ethanol/ammonia, gradient from 98:2:0.2 to 96:4:0.4) to give 4,4-dimethyl-2-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-4,5-dihydro-1,3-oxazole 15 (60 mg) as a beige powder.

Workup

  1. filtrationThe mixture is then filtered
  2. stirringthe mixture is again stirred under microwave irradiation, at 120° C. for another 1.5 h
  3. customThe solvent is then removed under vacuum
  4. additionthe residue diluted with ethyl acetate
  5. washThe organic layer is washed with water, with a saturated solution of sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe residue is purified over silicagel (eluent: dichloromethane/ethanol/ammonia, gradient from 98:2:0.2 to 96:4:0.4)

Sources & evidence

ORD record
ord-901da4901e6947cf986f9f3d21b82a19
Source dataset
uspto-grants-2011_01
Patent number
US07863450B2

Reaction notes

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