Malonic Acid → 3-(1-Cbz-4-piperidyl)acrylic Acid

HRID 458948Notes

Reaction equation

HRID 458948 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH:17]=O)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(=O)[CH2:20][C:21]([OH:23])=[O:22].N1C=CC=CC=1.N1CCCCC1>C(OCC)(=O)C>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([CH:17]=[CH:20][C:21]([OH:23])=[O:22])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 867Malonic AcidHCID 1049PyridineHCID 8082PiperidineHCID 2776272Benzyl 4-formylpiperidine-1-carboxylate

Product 1

HCID 693600903-(1-Cbz-4-piperidyl)acrylic Acid

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of N-benzyloxycarbonyl-4-formylpiperidine (10 g), malonic acid (4.2), pyridine (4 ml) and piperidine (0.4 ml) was heated at 100° C. for 2 hours. The reaction mixture was allowed to cool and was diluted with ethyl acetate (100 ml). The solution was washed with 2M HCl (2×100 ml), dried and evaporated to dryness. The residue was triturated with isohexane to give the title compound, yield 13.5 g. NMR (DMSOd6): 1.2 (m, 2H) 1.7 (m, 2H) 2.35 (m, 1H) 2.85 (m, 2H) 4 (d, 2H) 5.05 (s, 2H) 5.75 (d, 1H) 6.75 (m, 1H) 7.35 (m, 5H) 12.25 (broad peak, 1H)

Workup

  1. temperatureto cool
  2. washThe solution was washed with 2M HCl (2×100 ml)
  3. customdried
  4. customevaporated to dryness
  5. customThe residue was triturated with isohexane

Sources & evidence

ORD record
ord-52afdbd9c612479c850e7085eec218ce
Source dataset
uspto-grants-2007_03
Patent number
US07192973B2

Reaction notes

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