Methyl cyanoacetate → Tert-butyl 4-(1-cyano-2-methoxy-2-oxoethyl)benzoate

HRID 1919901Notes

Reaction equation

HRID 1919901 reaction equation
[C:1]([CH2:3][C:4]([O:6][CH3:7])=[O:5])#[N:2].Br[C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH:11][CH:10]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C1(C)C=CC=CC=1>[C:1]([CH:3]([C:9]1[CH:21]=[CH:20][C:12]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[CH:11][CH:10]=1)[C:4]([O:6][CH3:7])=[O:5])#[N:2]

Participants

6

Reactant 3

HCID 7747Methyl cyanoacetateHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 11334366Tert-butyl 4-bromobenzoate

Product 1

HCID 57611881Tert-butyl 4-(1-cyano-2-methoxy-2-oxoethyl)benzoate

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of Na3PO4 (9.84 g, 60.0 mmol), methyl cyanoacetate (2.38 g, 24.0 mmol), and tert-butyl 4-bromobenzoate (5.14 g, 20.0 mmol) were added Pd(dba)2 (575 mg, 1.00 mmol), toluene (60 mL), and P(t-Bu)3 (10% wt in hexanes, 11.56 mL, 3.89 mmol). After degassing for 20 minutes, the reaction was stirred at 80° C. for 16 h. The resulting mixture was diluted with EtOAc, washed with H2O and brine, dried (MgSO4), and concentrated. Flash chromatography on silica gel (0-15% EtOAc/hexanes) gave tert-butyl 4-(1-cyano-2-methoxy-2-oxoethyl)benzoate as a white solid. 1H NMR (CDCl3) δ8.02 (d, J=7.9 Hz, 2H), 7.51 (d, J=8.2 Hz, 2H), 4.79 (s, 1H), 3.79 (s, 3H), 1.58 (s, 9H). MS (ESI) calcd [M+H]+ 276.1, found 276.1.

Workup

  1. customAfter degassing for 20 minutes
  2. additionThe resulting mixture was diluted with EtOAc
  3. washwashed with H2O and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-be64590c208e4a7fb8e97a49fc99172e
Source dataset
uspto-grants-2012_05
Patent number
US08168658B2

Reaction notes

Loading…