Acetic Acid → HCID 67315281, compound

HRID 1012007Notes

Reaction equation

HRID 1012007 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[C:10]([CH3:16])([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24]C)=O.C(O)(=O)C.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])[O-].[K+].[K+].CCN=C=NCCCN(C)C.Cl>C(Cl)Cl.CO.CN(C=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([N:18]2[CH2:19][CH2:20][CH2:21][C:22]2=[O:24])[C:10]([CH3:16])([CH3:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

11

Reactant 7

HCID 176Acetic AcidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27563834-Aminobutyric acid methyl ester hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 97944131-Benzyl-3,3-dimethylpiperidin-4-one

Product 1

HCID 67315281HCID 67315281, compoundYield 85%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

To an ice cold solution of 1-benzyl-3,3-dimethyl-piperidin-4-one (0.5 g, 2 mmol) (J. Med. Chem. Lett. 2003, 13, 1627) in CH2Cl2 (10 ml) was added methyl 4-aminobutyrate hydrochloride (0.7 g, 5 mmol), acetic acid (0.4 ml, 7 mmol), triethylamine (0.5 ml, 5 mmol) and sodium triacetoxyborohydride (0.5 g, 3 mmol). The mixture was allowed to reach room temperature and was stirred for 16 h after which time it was washed with saturated sodium hydrogen carbonate solution, dried (Na2SO4) and concentrated. The residue (0.6 g, 2 mmol) was then redissolved in MeOH (10 ml), potassium carbonate (0.3 g, 2 mmol) added and the mixture heated to 70° C. for 2 h. The mixture was then filtered, the methanol evaporated and the residue redissolved in DMF (10 ml) and reacted with EDCl (0.4 g, 2 mmol) at 60° C. for 2 h after which time the DMF was evaporated, the residue taken up in CH2Cl2, washed with saturated sodium hydrogen carbonate solution, dried (Na2SO4) and concentrated. Flash column chromatography (EtOAc:n-heptane 2:1) afforded the title compound (0.4 g, 85%) as yellow oil. MS: 287.4 (MH+).

Workup

  1. customto reach room temperature
  2. washwas washed with saturated sodium hydrogen carbonate solution
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. filtrationThe mixture was then filtered
  6. customthe methanol evaporated
  7. dissolutionthe residue redissolved in DMF (10 ml)
  8. customwas evaporated
  9. washwashed with saturated sodium hydrogen carbonate solution
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-31d63f886f23436dafd6c1d91a19c9ee
Source dataset
uspto-grants-2011_07
Patent number
US07977358B2

Reaction notes

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