Potassium Carbonate → [Rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-ethoxy-phenyl}-2-ethoxy-propionic acid ethyl ester

HRID 1065013Notes

Reaction equation

HRID 1065013 reaction equation
[CH2:1]([O:3][C:4](=[O:20])[CH:5]([O:17][CH2:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=1[O:14][CH2:15][CH3:16])[CH3:2].[C:21]([C:25]1[CH:30]=[CH:29][C:28]([C:31]2[O:32][C:33]([CH3:38])=[C:34]([CH2:36]Cl)[N:35]=2)=[CH:27][CH:26]=1)([CH3:24])([CH3:23])[CH3:22].C(C1C=CC(C=O)=CC=1)(C)(C)C.O=P(Cl)(Cl)Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([O:17][CH2:18][CH3:19])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][CH2:36][C:34]2[N:35]=[C:31]([C:28]3[CH:27]=[CH:26][C:25]([C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:30][CH:29]=3)[O:32][C:33]=2[CH3:38])=[CH:9][C:8]=1[O:14][CH2:15][CH3:16])[CH3:2]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 24813Phosphorus oxychlorideHCID 703244-tert-ButylbenzaldehydeHCID 121582182-(4-Tert-butyl-phenyl)-4-chloromethyl-5-methyl-oxazoleHCID 68617228[Rac]-2-ethoxy-3-(2-ethoxy-4-hydroxy-phenyl)-propionic acid ethyl ester

Product 1

HCID 69279902[Rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-ethoxy-phenyl}-2-ethoxy-propionic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In analogy to the procedure described in example 1 f], [rac]-2-ethoxy-3-(2-ethoxy-4-hydroxy-phenyl)-propionic acid ethyl ester was reacted with 2-(4-tert-butyl-phenyl)-4-chloromethyl-5-methyl-oxazole (prepared from 4-tert-butyl-benzaldehyde and diacetyl monoxyme followed by treatment with POCl3 in analogy to the procedures described in examples 5 a] and 2 b]) in N,N-dimethylformamide in the presence of potassium carbonate to yield [rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-ethoxy-phenyl}-2-ethoxy-propionic acid ethyl ester, which was further saponified in analogy to the procedure described in example 1 g], to yield [rac]-3-{4-[2-(4-tert-butyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-2-ethoxy-phenyl}-2-ethoxy-propionic acid as colorless amorphous solid, which can be separated into its antipodes by methods known in the art, such as separation of the antipodes via diastereomeric salts by crystallization with optically pure amines such as e.g. (R) or (S)-1-phenyl-ethylamine, (R) or (S)-1-naphthalen-1-yl-ethylamine, brucine, quinine and quinidine or by separation of the antipodes by specific chromatographic methods using either a chiral adsorbens or a chiral eluent to give the title compound.

Sources & evidence

ORD record
ord-ae9c4e631b7642558c81182b388914d0
Source dataset
uspto-grants-2005_11
Patent number
US06969725B2

Reaction notes

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