Water → 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid potassium salt

HRID 418020Notes

Reaction equation

HRID 418020 reaction equation
[OH-].[K+:2].[OH:3][C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([O:13][C@@H:14]([CH3:18])[CH2:15][O:16][CH3:17])[CH:12]=1)[C:7]([OH:9])=[O:8].O.C1(C)C=CC=CC=1>C(O)CC>[K+:2].[OH:3][C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([O:13][C@@H:14]([CH3:18])[CH2:15][O:16][CH3:17])[CH:12]=1)[C:7]([O-:9])=[O:8]

Participants

6

Reactant 4

HCID 962WaterHCID 1140TolueneHCID 14797Potassium HydroxideHCID 576632243-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid

Product 1

HCID 666531343-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid potassium saltYield 93%

Reagents, catalysts & solvents 1

HCID 10311-PropanolSolvent

Conditions

Temperature
67 °C

Procedure

KOH liquor (1.04 eq. of 50.4 wt %) was added to a stirred, nitrogen sparged solution of 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1 eq.) in undried 1-propanol (4.87 vol.). At the end of the addition, water (0.33 vol.) and toluene (3.43 vol.) were separately added to the resulting slurry. The jacket temperature was raised to 67° C. before being subjected to the following cooling profile: 67° C. to 64° C. over 3 h, 64 to 57° C. over 3 h, 57 to 45° C. over 3 h, and 45 to 20° C. over 3 h. 6 h after the end of this ramp, the jacket temperature was lowered to 0° C. over 3 h, the jacket was foil wrapped and desupersaturation was allowed to complete overnight (>6 h). The slurry was isolated by filtration through an 11 micron filter paper. The cake was sequentially washed twice with an equal weight of an ice-cold solution of toluene (41.79 wt %) in 1-propanol. The cake was dried in a 40° C. house vacuum oven to give 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid potassium salt as tri-hydrate in a typical yield of 93% of theoretical yield.

Workup

  1. additionwere separately added to the resulting slurry
  2. temperaturefollowing cooling profile
  3. wait64 to 57° C. over 3 h
  4. wait57 to 45° C. over 3 h
  5. wait45 to 20° C. over 3 h
  6. wait6 h after the end of this ramp, the jacket temperature was lowered to 0° C. over 3 h
  7. waitdesupersaturation was allowed to complete overnight
  8. custom(>6 h)
  9. customThe slurry was isolated by filtration through an 11 micron
  10. filtrationfilter paper
  11. washThe cake was sequentially washed twice with an equal weight of an ice-cold solution of toluene (41.79 wt %) in 1-propanol
  12. customThe cake was dried in a 40° C. house vacuum oven

Sources & evidence

ORD record
ord-a21e9c5af49e4a68920ab70d6bd9d02e
Source dataset
uspto-grants-2012_01
Patent number
US08093252B2

Reaction notes

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