Hydrochloric Acid → [6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid

HRID 1644750노트

반응식

HRID 1644750 반응식
C[O:2][C:3](=[O:25])[CH2:4][C:5]1[C:14]([CH3:15])=[C:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:24])[CH:11]=2)[CH:6]=1.O.[OH-].[Li+].Cl>O1CCCC1.O>[F:24][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH:6]=[C:5]([CH2:4][C:3]([OH:25])=[O:2])[C:14]([CH3:15])=[C:13]2[CH2:16][C:17]1[CH:18]=[CH:19][C:20]([CH3:23])=[CH:21][CH:22]=1

참가 물질

6

반응물 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 59350825[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester

생성물 1

HCID 46206526[6-Fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid수율 60.5%

시약·촉매·용매 2

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매

실험 절차

A solution of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid methyl ester (140.8 mg, 0.419 mmol) in tetrahydrofuran (14 mL) was treated with a warm solution of lithium hydroxide monohydrate (175.8 mg, 4.19 mmol) in water (3.5 mL). The reaction mixture was stirred at room temperature for 20 hours, diluted with water, acidified with aqueous 3.0 N HCl and extracted with ethyl acetate. The ethyl acetate layers were combined, washed with brine, dried (MgSO4), filtered and concentrated. Purification by reverse phase HPLC gave 81.7 mg (60%) of [6-fluoro-3-methyl-4-(4-methyl-benzyl)-naphthalen-2-yl]-acetic acid as a white solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.43 (br. s, 1 H), 7.91 (dd, J=8.7, 6.3 Hz, 1 H), 7.74 (s, 1 H), 7.62 (dd, J=12.1, 1.8 Hz, 1 H), 7.33 (td, J=8.7, 1.8 Hz, 1 H), 7.03 (d, J=7.8 Hz, 2 H), 6.92 (d, J=7.8 Hz, 2 H), 4.40 (s, 2H), 3.82 (s, 2 H), 2.32 (s, 3 H), 2.21 (s, 3 H). HRMS (ES−) cald. for C21H19FO2 [(M−H)−] 321.1296, obsd. 321.1294.

후처리

  1. extractionextracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by reverse phase HPLC

출처 및 근거

ORD 기록
ord-fd8a2407489e45318b160a9c883ed7c8
출처 데이터셋
uspto-grants-2012_02
특허 번호
US08124629B2

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