Hydrochloric Acid → Di-tert-butyl 5-methylisophthalate

HRID 2222063

Reaction equation

HRID 2222063 reaction equation
[C:1](N1C=CN=C1)(N1C=CN=C1)=O.[C:13]1([CH3:25])[CH:18]=[C:17]([C:19]([OH:21])=[O:20])[CH:16]=[C:15]([C:22]([OH:24])=[O:23])[CH:14]=1.[CH2:26]1[CH2:36][CH2:35]N2C(=NCCC2)CC1.[CH3:37][C:38](O)([CH3:40])[CH3:39].Cl>CN(C=O)C.CCOCC>[C:13]1([CH3:25])[CH:18]=[C:17]([C:19]([O:21][C:38]([CH3:40])([CH3:39])[CH3:37])=[O:20])[CH:16]=[C:15]([C:22]([O:24][C:36]([CH3:35])([CH3:26])[CH3:1])=[O:23])[CH:14]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6386tert-ButanolHCID 681375-Methylisophthalic acidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene

Product 1

HCID 22610876Di-tert-butyl 5-methylisophthalateYield 84%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

1,1′-Carbonyldiimidazole (6.67 g, 0.0411 mol) was added to a solution of toluene-3,5-dicarboxylic acid (2) (3.364 g, 0.0187 mol) in DMF (30 mL) and the resulting mixture stirred at 40° C. under N2. After 1.5 h DBU (6.15 mL, 0.041 mol) and t-BuOH (7. 7 mL, 0.0822 mol) were added. After 24 h the solution was cooled, ether (150 mL) added and the mixture acidified (HCl (aq.), 1.5 M). The ethereal layer was separated and the aqueous layer further extracted (ether, 150 mL). The organic fractions were combined, washed with water and 10% K2CO3 (aq.), dried (MgSO4), filtered and the solvent removed. The residue was purified by flash chromatography (EtOAc:hexane, 1:50) to afford a colorless oil which solidified upon standing to give di-tert-butyl toluene-3,5-dicarboxylate (4.58 g, 84%) as a white solid; mp 86.5-87.5° C. (hexane); IR (film) 1712 cm−1 (C═O), 1606, 1476 cm−1 (Ar C═C); 1H NMR (CDCl3) δ 1.60 (s, 18H, C(CH3)3), 2.43 (s, 3H, CH3), 7.95 (br s, 2H, H-2, H-6), 8.38 (br s, 1H, H-4); 13C NMR (CDCl3) δ 21.4 (CH3), 28.2 (C(CH3)3), 81.4 (C(CH3)3), 127.7, 132.1, 133.7, 138.1 (Ar), 165.2 (COO).

Workup

  1. temperatureAfter 24 h the solution was cooled
  2. customThe ethereal layer was separated
  3. extractionthe aqueous layer further extracted (ether, 150 mL)
  4. washwashed with water and 10% K2CO3 (aq.)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent removed
  8. customThe residue was purified by flash chromatography (EtOAc:hexane, 1:50)
  9. customto afford a colorless oil which

Sources & evidence

ORD record
ord-f47ec98e60744e3291a422a27836be0f
Source dataset
uspto-grants-2008_05
Patent number
US07371553B2

Linked notes

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