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

HRID 898489노트

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HRID 898489 반응식
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]

참가 물질

7

반응물 5

HCID 342M-CresolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 235900072-{2-Bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid ethyl esterHCID 692322812-Methyl-2-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-2-m-tolyloxymethylphenoxy}propionic acid ethyl ester

생성물 1

HCID 222611642-{2-Bromomethyl-4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenoxy}-2-methylpropionic acid수율 84.3%

시약·촉매·용매 1

HCID 702Ethanol용매

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온도
80 °C

실험 절차

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).

후처리

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

출처 및 근거

ORD 기록
ord-1133a788175c43b184d3682a09bdadb3
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07351728B2

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