M-Cresol → 2-{2-Bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid

HRID 1609984Notes

Reaction equation

C([O:3][C:4](=[O:32])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[O:21][C:22]=2[CH3:23])=[CH:11][C:10]=1[CH2:30][Br:31])([CH3:7])[CH3:6])C.C1C(O)=CC=CC=1C.C(=O)([O-])[O-].[K+].[K+].C(OC(=O)C(C)(OC1C=CC(OCCC2N=C(C3C=CC=CC=3)OC=2C)=CC=1COC1C=C(C)C=CC=1)C)C.[OH-].[Na+]>C(O)C>[Br:31][CH2:30][C:10]1[CH:11]=[C:12]([O:15][CH2:16][CH2:17][C:18]2[N:19]=[C:20]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[O:21][C:22]=2[CH3:23])[CH:13]=[CH:14][C:9]=1[O:8][C:5]([CH3:7])([CH3:6])[C:4]([OH:32])=[O:3]

Participants

Conditions

Temperature: 80 °C

Procedure

The following example exemplifies the general procedure for the parallel synthesis of analogs utilizing the DynaVac carousel. To a 50 mL glass tube with screw cap and nitrogen inlet were charged 2-{2-bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl ester (0.040 g, 0.080 mmol), and 0.012 mL (0.12 mmol) of m-cresol dissolved in 1 mL of absolute ethanol, followed by the addition of powdered potassium carbonate (325 mesh) (0.022 g, 0.16 mmol). The mixture was heated to 80° C. for 4 h. MS analysis of the reaction indicated that 2-methyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-m-tolyloxymethylphenoxy}propionic acid ethyl ester, MS (ES) m/e 530 (M+1) had formed. Next 0.4 mL of 5N NaOH was added and the reaction was heated for 3 h at 55° C. The ethanol was removed in vacuo and the residue was treated with 0.75 mL of 5N HCl and 1 mL of MeCl2 and poured into a 3 mL ChemElute column to remove the aqueous layer. The column was eluted with additional MeCl2 until nothing UV active remained on the column. The solvent was removed in vacuo. The crude residue was purified by mass-directed reverse phase HPLC to provide 0.032 g (38%) of 2-{2-bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid, MS (ES) m/e 502 (M+1).

Workup

customfor the parallel synthesis of analogs
customTo a 50 mL glass tube with screw cap
customMS (ES) m/e 530 (M+1) had formed
temperaturethe reaction was heated for 3 h at 55° C
customThe ethanol was removed in vacuo
additionthe residue was treated with 0.75 mL of 5N HCl and 1 mL of MeCl2
additionpoured into a 3 mL ChemElute column
customto remove the aqueous layer
washThe column was eluted with additional MeCl2 until nothing UV
customThe solvent was removed in vacuo
customThe crude residue was purified by mass-directed reverse phase HPLC

Sources & evidence

ORD record: ord-2c767fdc2e5b439a94e1ccffe946665c
Source dataset: uspto-grants-2006_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06982278B2

Reaction notes

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