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Ethyl Acetate → Ethyl 2-(4-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetate

HRID 2175282
ノート
印刷プレビュー

反応式

HRID 2175282 の反応式
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][CH2:6][N:7]2[C:12](=[O:17])[CH2:13][CH2:14][CH2:15][OH:16].CC1(C)C(C)(C)OB([C:26]2[CH:27]=[N:28][N:29]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:30]=2)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(OCC)(=O)C>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CO>[OH:16][CH2:15][CH2:14][CH2:13][C:12]([N:7]1[C:8]2[C:3](=[C:2]([C:26]3[CH:27]=[N:28][N:29]([CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH:30]=3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][CH2:6]1)=[O:17]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 162183851-(Ethoxycarbonylmethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 709827651-(5-Bromo-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutan-1-one

生成物 1

HCID 70983434Ethyl 2-(4-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)-1H-pyrazol-1-yl)acetate収率 94.5%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
80 °C

実験手順

To a degassed solution of 1-(5-bromo-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutan-1-one (68 mg, 0.228 mmol), ethyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)acetate (80 mg, 0.285 mmol) and potassium phosphate (145 mg, 0.684 mmol) in THF (1 mL) was added PdCl2(dppf) (15 mg, 0.021 mmol). The vial was purged with argon, sealed, and stirred 80° C. overnight. After this time, the reaction mixture was partitioned between EtOAc and saturated NH4Cl solution, and the organic layer was separated. The aqueous phase was extracted with EtOAc. The combined organic layers were dried over anhydrous MgSO4, filtered, and concentrated in vacuo to provide the crude material. The crude material was purified by flash chromatography (0-100% ethyl acetate:hexanes then 10% ethyl acetate:MeOH) to afford the title compound (80 mg, 85% yield) as a yellow oil. LCMS, [M+H]+=372.1. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.53 (s, 1H), 7.23-7.12 (m, 3H), 4.94 (s, 2H), 4.25 (q, J=7.1 Hz, 2H), 3.78 (t, J=6.9 Hz, 2H), 3.68 (dd, J=11.1, 5.5 Hz, 2H), 2.73 (t, J=6.5 Hz, 2H), 2.64 (t, J=6.7 Hz, 2H), 1.97-1.83 (m, 4H), 1.29 (t, J=7.1 Hz, 3H).

後処理

  1. customThe vial was purged with argon
  2. customsealed
  3. customAfter this time, the reaction mixture was partitioned between EtOAc and saturated NH4Cl solution
  4. customthe organic layer was separated
  5. extractionThe aqueous phase was extracted with EtOAc
  6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto provide the crude material
  10. customThe crude material was purified by flash chromatography (0-100% ethyl acetate

出典と根拠

ORDレコード
ord-b355283c78cc4aceb7c056c462aae124
出典データセット
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09062028B2

反応ノート

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