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

HRID 2247681ノート

反応式

HRID 2247681 の反応式
[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]

参加物

9

反応物 6

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-22bae57b4d7a486cbec2ccde0adf22b2
出典データセット
uspto-grants-2010_03
特許番号
US07687491B2

反応ノート

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