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

HRID 2175282Notes

Reaction equation

HRID 2175282 reaction equation
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]

Participants

8

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-b355283c78cc4aceb7c056c462aae124
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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