Hydrochloric Acid → 2-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid methyl ester

HRID 553448

반응식

HRID 553448 반응식
[CH3:1][O:2][C:3](=[O:13])[CH:4]([NH2:12])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].[F:14][C:15]1[CH:16]=[C:17](B(O)O)[CH:18]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:20]=1.C(N(CC)CC)C.Cl>C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH3:1][O:2][C:3](=[O:13])[CH:4]([NH:12][C:17]1[CH:16]=[C:15]([F:14])[CH:20]=[C:19]([C:21]([F:23])([F:24])[F:22])[CH:18]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 27831923-Fluoro-5-(trifluoromethyl)benzeneboronic acidHCID 76642825Methyl 2-aminonon-8-enoate

생성물 1

HCID 669153962-(3-Trifluoromethyl-5-fluoro-phenylamino)-non-8-enoic acid methyl ester수율 206.9%

시약·촉매·용매 2

HCID 8895Cupric acetate촉매HCID 6344Dichloromethane용매

실험 절차

Reaction performed in parallel in 8×50 mL reaction flasks. Copper (II) acetate (270 mg, 1.48 mmol., 1.1 eq.) and 4 Å molecular sieves (700 mg) were charged in 50 mL round bottom flask. Dichloromethane (10 mL, previously saturated with air) was added a single portion. 2-amino-non-8-enoic acid methyl ester (250 mg, 1.35 mmol., 1.0 eq.) was added and the reaction mixture was stirred for a further 5 min by when the initial light blue solution had turned dark blue. 3-fluoro-5-trifluoromethylbenzene boronic acid (560 mg, 2.70 mmol., 2 eq.) was added followed by triethylamine (218 mg, 2.70 mmol., 2 eq.). The reaction mixture was stirred over night under an air atmosphere. The 8 reaction mixtures were combined together and 1M hydrochloric acid (150 mL) was added. The mixture was stirred for a further 5 min until the aqueous layer turned pale blue and the organic layer turned pale yellow. The organic layer was collected, dried over sodium sulfate and the solvent removed under vacuum. The residue was purified by flash column chromatography, using a dichloromethane:heptanes gradient (from neat heptane to 50% dichloromethane in heptanes). After combining the relevant fractions and solvent removal, 970 mg (26%) of the title compound was isolated as a yellow oil. 1H NMR (500 MHz, CDCl3) δ ppm 6.66 (d, J=8.54 Hz, 1 H), 6.61 (s, 1 H), 6.42 (d, J=10.83 Hz, 1 H), 5.72-5.87 (m, J=6.71, 6.71, 10.26, 17.05 Hz, 1 H), 5.00 (dd, J=1.83, 17.09 Hz, 1 H), 4.95 (dt, J=0.95, 10.15 Hz, 1 H), 4.48 (d, J=8.54 Hz, 1 H), 4.05 (dt, J=6.45, 8.32 Hz, 1 H), 3.76 (s, 3H), 2.05 (q, J=6.92 Hz, 2 H), 1.82-1.93 (m, 1 H), 1.71-1.82 (m, 1 H), 1.30-1.45 (m, 6 H). LC-MS: purity 94% (UV), tR 2.63 min, m/z [M+H]+ 348.00.

후처리

  1. customReaction
  2. customparallel in 8×50 mL reaction flasks
  3. stirringThe reaction mixture was stirred over night under an air atmosphere
  4. customThe 8 reaction mixtures
  5. stirringThe mixture was stirred for a further 5 min until the aqueous layer
  6. customThe organic layer was collected
  7. dry with materialdried over sodium sulfate
  8. customthe solvent removed under vacuum
  9. customThe residue was purified by flash column chromatography
  10. customthe relevant fractions and solvent removal

출처 및 근거

ORD 기록
ord-6b43e1eb2da546628b83f84934c92e3c
출처 데이터셋
uspto-grants-2011_11
특허 번호
US08048862B2

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