Methyl cyanoacetate → HCID 131721341, compound

HRID 1585460Notes

Reaction equation

HRID 1585460 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH:7](C)[CH2:8][CH:9]=O.[C:12]([CH2:14][C:15]([O:17][CH3:18])=[O:16])#[N:13]>C(O)(=O)C.N1CCCCC1>[C:12](/[C:14](=[CH:9]\[CH2:8][CH2:7][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][N:1]=1)/[C:15]([O:17][CH3:18])=[O:16])#[N:13]

Participants

5

Reactant 2

HCID 7747Methyl cyanoacetateHCID 21919386HCID 21919386, compound

Product 1

HCID 131721341HCID 131721341, compoundYield 35.5%

Reagents, catalysts & solvents 2

HCID 8082PiperidineCatalystHCID 176Acetic AcidSolvent2×

Procedure

A solution of 13e (0.191 g, 1.27 mmol) in 0.17 mL glacial acetic acid was treated with NCCH2CO2CH3 (0.115 g, 1.27 mmol, 0.1 mL, 1.0 equiv), then a premixed solution of piperidine (0.0038 g, 0.04318 mmol, 4.4 mL, 3.4 mol %) and 50 mL of acetic acid at room temperature (24 h). The reaction mixture was quenched by the addition of saturated aqueous NaHCO3 (15 mL, pH>7) and extracted with EtOAc (3×15 mL). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. SGC chromatotron (SiO2, 1 mm, 25-65% EtOAc/hexanes) afforded 15e (0.098 g, 0.282 g theoretical, 35%). For 15e: 1H NMR (CDCl3, 400 MHz) d 8.52 (dd, 1H, J=1.6, 2.5 Hz, Pyr C5-H), 8.46 (d, 1H, J=1.6 Hz, Pyr C3-H), 8.44 (d, 1H, J=2.5 Hz, Pyr C6-H), 7.59 (dd, 1H, J=7.8, 7.8 Hz, CH=C), 3.82 (s, 3H, OCH3), 3.23 (ddq, 1H, J=6.4, 7.0, 7.2 Hz, PyrCH), 3.07 (ddd, 1H, J=7.2, 7.8, 14.9 Hz, CHH), 2.91 (ddd, 1H, J=6.4, 7.8, 14.6 Hz, CHH), 1.39 (d, 3H, J=7.0 Hz, CH3); IR (neat) nmax 2967, 2360, 2341, 1737, 1626, 1437, 1407, 1282, 1259, 1060, 1017, 850, 761, 668 cm-. See FIG. 19d.

Workup

  1. customat room temperature
  2. custom(24 h)
  3. customThe reaction mixture was quenched by the addition of saturated aqueous NaHCO3 (15 mL, pH>7)
  4. extractionextracted with EtOAc (3×15 mL)
  5. dry with materialThe combined organic extracts were dried (MgSO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6d004f273ef1434b94cbbbf1a4537bdc
Source dataset
uspto-grants-1999_08
Patent number
US05939268

Reaction notes

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