Acetic Acid → HCID 67196651, compound

HRID 547904Notes

Reaction equation

HRID 547904 reaction equation
[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH2:11])[CH:2]=1.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(O)(=O)C.ClC(Cl)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[Na+].[Cl-]>[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][CH:22]([NH:11][C:3]2[CH:2]=[N:1][C:10]3[C:5]([CH:4]=2)=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 63651,1-DichloroethaneHCID 113753-AminoquinolineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 67196651HCID 67196651, compoundYield 56%

Reagents, catalysts & solvents 1

HCID 5234Sodium ChlorideSolvent

Procedure

A mixture of quinolin-3-ylamine (3.62 g, 25.09 mmol, 1.0 equiv, commercially available) and 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (5.00 g, 25.09 mmol, 1.0 equiv; commercially available) in conc. acetic acid (1.44 mL, 1.51 g, 25.09 mmol, 1.0 equiv) and dichloroethane (50 mL) was stirred at rt for 4 h. Sodium triacetoxyborohydride (6.38 g, 30.11 mmol, 1.2 equiv) was added in one portion and the reaction mixture stirred for an additional time period of 16 h. To the reaction mixture was added a sat. solution of NaCl (2×50 mL) and the crude extracted with ethyl acetate (3×100 mL). The combined organic phases were washed over a sat. solution of Na2CO3 (50 mL), dried over MgSO4, concentrated by evaporation under reduced pressure and the crude material purified with silica column chromatography eluting with a gradient of dichloromethane/methanol (10:1→9:1). Trituration from heptane/ethyl acetate provided 4.60 g (56%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.36-1.46 (m, 2H), 1.49 (s, 9H), 2.12 (d, J=10.5 Hz, 2H), 3.00 (t, J=11.9 Hz, 2H), 3.47-3.64 (m, 1H), 3.89 (d, J=7.7 Hz, 1H), 4.10 (br s, 2H), 7.03 (d, J=2.7 Hz, 1H), 7.37-7.47 (m, 2H), 7.59-7.64 (m, 1H), 7.89-7.98 (m, 1H), 8.42 (d, J=2.7 Hz, 1H).

Workup

  1. extractionthe crude extracted with ethyl acetate (3×100 mL)
  2. washThe combined organic phases were washed over a sat. solution of Na2CO3 (50 mL)
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated by evaporation under reduced pressure
  5. customthe crude material purified with silica column chromatography
  6. washeluting with a gradient of dichloromethane/methanol (10:1→9:1)

Sources & evidence

ORD record
ord-fe7e887260c44266b61f1564780e890a
Source dataset
uspto-grants-2011_05
Patent number
US07939661B2

Reaction notes

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