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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
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HRID 2175282 반응식
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]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 887Methanol용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b355283c78cc4aceb7c056c462aae124
출처 데이터셋
uspto-grants-2015_06
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09062028B2

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