Phenylacetic Acid → HCID 86754755, compound

HRID 1601659Notes

Reaction equation

HRID 1601659 reaction equation
ClC1C(Cl)=CC=CC=1C=O.[C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(OC)(=O)CC(C)=O.[CH3:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(O)(C)C>[C:11]1([CH2:17][C:18]([OH:20])=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[CH3:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 999Phenylacetic AcidHCID 7669N-MethylbenzylamineHCID 7757Methyl acetoacetateHCID 357452,3-Dichlorobenzaldehyde

Product 1

HCID 86754755HCID 86754755, compoundYield 62.4%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
2.5 °C

Procedure

A single necked 1-L flask charged with 2,3-dichlorobenzaldehyde (87.5 g, 0.5 mol), phenylacetic acid (4.08 g, 0.030 mol), isopropanol (662 mL), methyl acetoacetate (64.0 g, 0.55 mol), and N-methylbenzylamine (3.6 g, 0.030 mol). The flask was placed on a rotary evaporator equipped with a thermowell (via steam duct) for monitoring internal temperature and the flask heated and agitated to bring flask contents up to 55-65° C. for approximately 4-5 hours. The mixture was concentrated by removing 250-350 g of distillate at about 45-65° C. (internal temperature) and the contents gradually cooled in an ice bath to about 0-5° C. The precipitated MBI solids were isolated by filtration and washed with about isopropanol (75-80 g). The washings were combined with the filtrate. The combined filtrates and washings were re-heated to 55-65° C. for one hour, and concentrated by removing about 175-225 g of the distillate at about 45-65° C. (internal temperature). The contents were again gradually cooled in an ice bath to collect a second crop of MBI solids which were isolated by filtration on the same filter funnel containing the first crop of solids. The combined first and second crop solids were washed with 4×80 g of isopropanol and dried in vacuo at ambient temperature. This gave MBI as a white solid (85.2 g, 62.4% Yield based on dichlorobenzaldehyde). LC analysis showed 99.91% MBI [97.63% A-isomer+2.28% B-isomer].

Workup

  1. customThe flask was placed on a rotary evaporator
  2. customequipped with a thermowell (via steam duct)
  3. temperaturethe flask heated
  4. customup to 55-65° C.
  5. customfor approximately 4-5 hours
  6. concentrationThe mixture was concentrated
  7. customby removing 250-350 g of distillate at about 45-65° C. (internal temperature)
  8. customThe precipitated MBI solids were isolated by filtration
  9. washwashed with about isopropanol (75-80 g)
  10. temperatureThe combined filtrates and washings were re-heated to 55-65° C. for one hour
  11. concentrationconcentrated
  12. customby removing about 175-225 g of the distillate at about 45-65° C. (internal temperature)
  13. temperatureThe contents were again gradually cooled in an ice bath
  14. customto collect a second crop of MBI solids which
  15. customwere isolated by filtration on the same filter funnel
  16. additioncontaining the first crop of solids
  17. washThe combined first and second crop solids were washed with 4×80 g of isopropanol
  18. customdried in vacuo at ambient temperature

Sources & evidence

ORD record
ord-e45d3a4f15e542f7a9885f390f503471
Source dataset
uspto-grants-1999_11
Patent number
US05977369

Reaction notes

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