Carbon tetrabromide → Ethyl 1-({4-[3-(4-isobutylphenyl)isoxazol-5-yl]-2-thienyl}methyl)azetidine-3-carboxylate

HRID 2247681노트

반응식

HRID 2247681 반응식
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH2:21]O)[S:19][CH:20]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].C(Br)(Br)(Br)Br.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl.[NH:48]1[CH2:51][CH:50]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:49]1.C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>ClCCl.O>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[CH:15]=[C:14]([C:16]3[CH:17]=[C:18]([CH2:21][N:48]4[CH2:51][CH:50]([C:52]([O:54][CH2:55][CH3:56])=[O:53])[CH2:49]4)[S:19][CH:20]=3)[O:13][N:12]=2)=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3]

참가 물질

9

반응물 6

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 44828820Ethyl azetidine-3-carboxylate hydrochlorideHCID 68521914{4-[3-(4-Isobutylphenyl)isoxazol-5-yl]-2-thienyl}methanol

생성물 1

HCID 68525245Ethyl 1-({4-[3-(4-isobutylphenyl)isoxazol-5-yl]-2-thienyl}methyl)azetidine-3-carboxylate수율 82%

시약·촉매·용매 2

HCID 962Water용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

A solution of {4-[3-(4-isobutylphenyl)isoxazol-5-yl]-2-thienyl}methanol (0.43 g, 1.4 mmol) that was obtained in Example 9 (9g), carbon tetrabromide (0.68 g, 2.1 mmol) and triphenylphosphine (0.54 g, 2.1 mmol) in dichloromethane (15 ml) was stirred at 0° C. for 5 minutes. Subsequently, to the reaction mixture were added successively ethyl 3-azetidinecarboxylate hydrochloride (0.34 mg, 2.1 mmol) and N,N-diisopropylethylamine (0.60 ml, 3.4 mmol) with stirring, and the resulting mixture was stirred at room temperature for 18 hours. After stirring, a saturated aqueous solution of sodium hydrogencarbonate (5 ml) was added to the reaction mixture to quench the reaction, and the resulting mixture was poured into water (50 ml) and extracted with dichloromethane. The extract was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:4 to 3:2) as the eluent to afford the title compound (0.48 g) in a yield of 82% as a white crystalline solid.

후처리

  1. stirringwith stirring
  2. stirringthe resulting mixture was stirred at room temperature for 18 hours
  3. stirringAfter stirring
  4. customto quench
  5. customthe reaction
  6. extractionextracted with dichloromethane
  7. washThe extract was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. filtrationAfter filtration
  10. customthe filtrate was evaporated in vacuo

출처 및 근거

ORD 기록
ord-22bae57b4d7a486cbec2ccde0adf22b2
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07687491B2

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