Cyanoacetic acid → HCID 59385358, compound

HRID 2356840Notes

Reaction equation

HRID 2356840 reaction equation
[C:1]([CH2:3][C:4]([OH:6])=O)#[N:2].C([Mg]Cl)(C)C.[C:12]([O:16][C:17]([N:19]1[CH2:24][CH2:23][C:22]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)(C(O)=O)[CH2:21][CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13].C(N1C=CN=C1)(N1C=CN=C1)=O>C1COCC1.CC(O)=O.O>[C:12]([O:16][C:17]([N:19]1[CH2:20][CH2:21][C:22]([C:4](=[O:6])[CH2:3][C:1]#[N:2])([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:23][CH2:24]1)=[O:18])([CH3:15])([CH3:13])[CH3:14]

Participants

8

Reactant 4

HCID 9740Cyanoacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 7369171-((Tert-butoxy)carbonyl)-4-phenylpiperidine-4-carboxylic acidHCID 178418918HCID 178418918, compound

Product 1

HCID 59385358HCID 59385358, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 2.52 g (30 mmol) of cyanoacetic acid in 80 mL of dry THF was stirred at −78° C. as 24.6 mL (49.2 mmol) of 2.0 M i-PrMgCl in THF was added. After 1 h, a solution of 3.00 g (10 mmol) 1-tert-butoxycarbonyl-4-phenylpiperidine-4-carboxylic acid (Maybridge, cat. no. JFD 01929) and 1.93 g (12 mmol) of 1,1′-carbonyldiimidazole in 20 mL of THF was added. The reaction mixture was allowed to warm to rt. After 16 h, the mixture was poured into 300 mL of water and the pH lowered to 4 with conc. AcOH. The mixture was then extracted with EtOAc, dried over MgSO4 and concentrated. Purification on silica gel using 1:1 EtOAc-hexanes as eluant afforded 4-(2-cyanoacetyl)-4-phenylpiperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. additionwas added
  2. waitAfter 16 h
  3. extractionThe mixture was then extracted with EtOAc
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customPurification on silica gel using 1:1 EtOAc-hexanes as eluant

Sources & evidence

ORD record
ord-c2e87632a2a74acc9ea9b077175a0173
Source dataset
uspto-grants-2010_07
Patent number
US07759382B2

Reaction notes

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