Dimethyl malonate → Dimethyl [4-(tert-butoxycarbonyl)phenyl]malonate

HRID 1694827Notes

Reaction equation

HRID 1694827 reaction equation
Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:23]([O:30][CH3:31])(=[O:29])[CH2:24][C:25]([O:27][CH3:28])=[O:26].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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[C:9]([O:8][C:6]([C:5]1[CH:13]=[CH:14][C:2]([CH:24]([C:23]([O:30][CH3:31])=[O:29])[C:25]([O:27][CH3:28])=[O:26])=[CH:3][CH:4]=1)=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 7943Dimethyl malonateHCID 62657Potassium Phosphate, TribasicHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 11334366Tert-butyl 4-bromobenzoate

Product 1

HCID 57541233Dimethyl [4-(tert-butoxycarbonyl)phenyl]malonate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a mixture of tert-butyl 4-bromobenzoate (10.07 g, 39.2 mmol), K3PO4 (20.19 g, 95 mmol), and dimethyl malonate (4.50 mL, 39.2 mmol) was added toluene (69 mL), Pd2(dba)3 (975 mg, 1.08 mmol), and P(tert-Bu)3 (12.8 mL, 10% wt. in hexanes, 4.3 mmol). The reaction mixture was degassed and heated to 85° C. After 2 d, the reaction mixture was diluted with ethyl acetate, washed with water (1×), brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (5% to 20% ethyl acetate in hexanes) gave dimethyl [4-(tert-butoxycarbonyl)phenyl]malonate as a low melting white solid: 1H NMR (600 MHz, CDCl3) δ 7.98 (d, J=8.5 Hz, 2H), 7.45 (d, J=8.2 Hz, 2H), 4.70 (s, 1H), 3.76 (s, 6H), 1.58 (s, 91-1); ESIMS calcd 331.1 (M++Na), found 331.1 (M++Na). General Procedure for the Amidation of Dimethyl [4-(tert-butoxycarbonyl)phenyl]malonate

Workup

  1. customThe reaction mixture was degassed
  2. additionthe reaction mixture was diluted with ethyl acetate
  3. washwashed with water (1×), brine (1×)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by flash column chromatography on silica gel (5% to 20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-bc3b162dbb2d42dea3dffb09830bb218
Source dataset
uspto-grants-2012_04
Patent number
US08158825B2

Reaction notes

Loading…