Sodium Carbonate → tert-Butyl 3-((3-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyloxy)carbonylamino)propanoate

HRID 2175284Notes

Reaction equation

HRID 2175284 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(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].Br[C:42]1[CH:43]=[C:44]([CH:59]=[CH:60][CH:61]=1)[CH2:45][O:46][C:47]([NH:49][CH2:50][CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])=[O:48].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.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].C(Cl)Cl.C(OCC)(=O)C.CO>[OH:16][CH2:15][CH2:14][CH2:13][C:12]([N:7]1[C:8]2[C:3](=[C:2]([C:42]3[CH:43]=[C:44]([CH:59]=[CH:60][CH:61]=3)[CH2:45][O:46][C:47]([NH:49][CH2:50][CH2:51][C:52]([O:54][C:55]([CH3:57])([CH3:58])[CH3:56])=[O:53])=[O:48])[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][CH2:6]1)=[O:17]

Participants

10

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 709827651-(5-Bromo-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutan-1-oneHCID 70982800tert-Butyl 3-((3-bromobenzyloxy)carbonylamino)propanoate

Product 1

HCID 70982571tert-Butyl 3-((3-(1-(4-hydroxybutanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyloxy)carbonylamino)propanoateYield 69.2%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalyst2×HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed mixture of 1-(5-bromo-3,4-dihydroquinolin-1(2H)-yl)-4-hydroxybutan-1-one (0.208 g, 0.698 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (0.532 g, 2.094 mmol), and potassium acetate (0.411 g, 4.19 mmol) in DMF (10 mL) was added PdCl2(dppf)-CH2Cl2 (0.057 g, 0.070 mmol). The vial was purged with argon, sealed, and stirred at 90° C. for 2 d. tert-Butyl 3-((3-bromobenzyloxy)carbonylamino)propanoate (0.5 g, 1.396 mmol), PdCl2(dppf)-CH2Cl2 (0.057 g, 0.070 mmol), and 2 M Na2CO3 (2 mL, 1.396 mmol) were added. The reaction mixture was purged with argon and stirred at 95° C. overnight. At the conclusion of this period, the reaction mixture was quenched with water and extracted with ethyl acetate. The organic extract was dried, concentrated, and purified by flash chromatography (0-100% ethyl acetate:hexanes then 10% CH3OH:ethyl acetate) to afford the title compound (0.24 g, 69% yield) as a dark brown oil. LCMS, [M+H]+=497.4.

Workup

  1. customThe vial was purged with argon
  2. customsealed
  3. customThe reaction mixture was purged with argon
  4. stirringstirred at 95° C. overnight
  5. customAt the conclusion of this period, the reaction mixture was quenched with water
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. customwas dried
  9. concentrationconcentrated
  10. custompurified by flash chromatography (0-100% ethyl acetate

Sources & evidence

ORD record
ord-1ecb485f1753467490a67e676da99f76
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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