Methanol → Benzoic acid, 2-iodo-5-methyl-, methyl ester

HRID 1045990Notes

Reaction equation

HRID 1045990 reaction equation
[I:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[OH-].[Na+].[CH3:19]O>>[I:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([O:6][CH3:19])=[O:5]

Participants

5

Reactant 4

HCID 887MethanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 1429412-Iodo-5-methylbenzoic acid

Product 1

HCID 14263946Benzoic acid, 2-iodo-5-methyl-, methyl esterYield 98%

Conditions

Temperature
16 °C

Procedure

A visually clean 100 L flask equipped with a mechanical stirrer thermocouple and water chilled condenser was charged with MeOH (50 L). 2-iodo-5-methylbenzoic acid (5.85 kg, 22.32 mol) was then added while stirring. Concentrated sulfuric acid (0.595 L, 11.16 mol) was then added portion-wise which caused an increase in temperature from 17° C. to 22° C. This mixture was gradually brought to an internal temperature of 64.6° C. an aged overnight (˜18 h). The next morning the reaction had reached >98% conversion by HPLC. The flask was cooled to 16° C. by placing in an ice bath and 850 ml of 10N NaOH (0.98 equiv.) was added slowly (over 10 minutes) while monitoring the pH. After the addition the pH was 5-6 (Caution: bringing pH over 9 can result in saponification during the work-up). The solution was then concentrated to about 16 L and this suspension was transferred to a 100 L extractor. The flask was rinsed with 8 L of IPAc and 4 L of water which were also transferred to the extractor. 32 L IPAc along with 10 L of 5 w % NaHCO3 and ˜10 L of 15 w % Brine. The layers were cut and the aqueous layers were back-extracted with 20 L of IPAc. The organic layers were then combined and washed with 10 L of 15 w % Brine. The organic layers were collected to provide E-1 (6.055 kg, 21.93 mol, 98% yield) in 98.3% purity.

Workup

  1. customA visually clean 100 L flask equipped with a mechanical stirrer thermocouple and water chilled condenser
  2. temperaturean increase in temperature from 17° C. to 22° C
  3. custom(˜18 h)
  4. customby placing in an ice bath
  5. additionAfter the addition the pH was 5-6 (Caution
  6. customcan result in saponification during the work-up)
  7. concentrationThe solution was then concentrated to about 16 L
  8. washThe flask was rinsed with 8 L of IPAc and 4 L of water which
  9. extractionthe aqueous layers were back-extracted with 20 L of IPAc
  10. washwashed with 10 L of 15 w % Brine
  11. customThe organic layers were collected
  12. customto provide E-1 (6.055 kg, 21.93 mol, 98% yield) in 98.3% purity

Sources & evidence

ORD record
ord-990f728fad4641fcbfa3d9ddb8b97376
Source dataset
uspto-grants-2013_10
Patent number
US08569311B2

Reaction notes

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