Trimethylaluminum → 3-(4-{[5-(4-Chloro-phenyl)-3-(2-hydroxy-ethyl)-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester

HRID 2384902ノート

反応式

HRID 2384902 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH2:19])=[CH:15][C:14]=2[O:20][CH3:21])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[Al](C)C.[Cl:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:42][C:36]3[C:37](=[O:41])[O:38][CH2:39][CH2:40][C:35]=3[CH:34]=2)=[CH:29][CH:28]=1>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH:10]([O:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:37]([C:36]3[S:42][C:33]([C:30]4[CH:29]=[CH:28][C:27]([Cl:26])=[CH:32][CH:31]=4)=[CH:34][C:35]=3[CH2:40][CH2:39][OH:38])=[O:41])=[CH:15][C:14]=2[O:20][CH3:21])[CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 16682925TrimethylaluminumHCID 46835556Tert-butyl 3-(4-amino-2-methoxyphenoxy)azetidine-1-carboxylateHCID 689489532-(4-Chloro-phenyl)-4,5-dihydro-thieno[2,3-c]pyran-7-one

生成物 1

HCID 689523253-(4-{[5-(4-Chloro-phenyl)-3-(2-hydroxy-ethyl)-thiophene-2-carbonyl]-amino}-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester収率 99.5%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

実験手順

Dissolve 3-(4-amino-2-methoxy-phenoxy)-azetidine-1-carboxylic acid tert-butyl ester (2.27 mmol, 667 mg) in toluene (35 mL) and add 2M trimethylaluminum in toluene (2.27 mmol 1.13 mL). Add to this solution 2-(4-chloro-phenyl)-4,5-dihydro-thieno[2,3-c]pyran-7-one (1.51 mmol 400 mg) and heat the reaction at 80° C. for 5 h. Cool the reaction to room temperature and slowly quench with 10 mL of saturated Rochelle's salt. Stir the mixture for 10 min and dilute with 40 mL of water. Separate the organic portion and extract the aqueous portion with EtOAc (2×25 mL). Dry the combined organics over Na2SO4, filter, and concentrate to dryness. Purify by chromatography (hexane to 70% ethyl acetate/hexane) to afford 840 mg (99%) of the title compound. MS/ES m/z (35Cl) 557.0 [M−H]−.

後処理

  1. temperatureheat
  2. customthe reaction at 80° C. for 5 h
  3. temperatureCool
  4. customthe reaction to room temperature
  5. customslowly quench with 10 mL of saturated Rochelle's salt
  6. additiondilute with 40 mL of water
  7. customSeparate the organic portion
  8. extractionextract the aqueous portion with EtOAc (2×25 mL)
  9. dry with materialDry the combined organics over Na2SO4
  10. filtrationfilter
  11. concentrationconcentrate to dryness
  12. customPurify by chromatography (hexane to 70% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-4215903d65704bcfb2e472254e24f7af
出典データセット
uspto-grants-2012_09
特許番号
US08263772B2

反応ノート

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