Water → HCID 11001934, compound

HRID 893095Notes

Reaction equation

HRID 893095 reaction equation
[CH2:1]([CH:8]([CH2:13][S:14]([N:17]1[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]1)(=[O:16])=[O:15])[C:9]([O:11]C)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Na+].C(O)(C)C>CC(C)=O>[CH2:1]([C@H:8]([CH2:13][S:14]([N:17]1[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]1)(=[O:16])=[O:15])[C:9]([OH:11])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 3776IsopropanolHCID 14798Sodium Hydroxide2×HCID 22402988Methyl α-[[(4-methyl-1-piperazinyl)sulfonyl]methyl]benzenepropanoate

Product 1

HCID 11001934HCID 11001934, compoundYield 199.1%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
75 °C

Procedure

The product of Example 6B (69 kg, 20 mol) in acetone (420 kg)/water (960 kg) was adjusted to pH 8.0 using 1N sodium hydroxide. Alcalase ™ (Subtilisin) was added and the pH was maintained between 7.9 and 8.4 by the addition of 1N sodium hydroxide. When 80% of the theoretical amount of sodium hydroxide had been consumed, the reaction was quenched by the addition of ethyl acetate. The reaction mixture was concentrated to half the original volume under reduced pressure and then washed with ethyl acetate (2 ×700 kg). The volume of the aqueous phase was concentrated by half and the pH adjusted to 5.2. The reaction mixture was treated with XAD-16 resin (50 kg), stirred for 18 hours, and applied to an XAD-16 resin column (50 kg). The column was eluted with water (500 kg) and then 35% ethanol in water (1000 kg) to afford a residue which was treated with isopropanol (270 kg) and warmed to 75° C. Upon cooling to room temperature and subsequently to -5° C., crystalline material was obtained. The solid was removed by filtration, washed with cold isopropanol (30 kg) and dried at 50° C. to afford the title compound (13 kg, 49%). The 30 MHz 1H NMR spectrum was found to be consistent with the proposed structure. MS (DCI/NH3) m/e 327 (M+H)+. This compound could be recrystallized from 1:1 isopropanol/water.

Workup

  1. additionAlcalase ™ (Subtilisin) was added
  2. customWhen 80% of the theoretical amount of sodium hydroxide had been consumed
  3. customthe reaction was quenched by the addition of ethyl acetate
  4. concentrationThe reaction mixture was concentrated to half the original volume under reduced pressure
  5. washwashed with ethyl acetate (2 ×700 kg)
  6. concentrationThe volume of the aqueous phase was concentrated by half
  7. additionThe reaction mixture was treated with XAD-16 resin (50 kg)
  8. washThe column was eluted with water (500 kg)
  9. custom35% ethanol in water (1000 kg) to afford a residue which
  10. temperatureUpon cooling to room temperature and subsequently to -5° C.
  11. customcrystalline material was obtained
  12. customThe solid was removed by filtration
  13. washwashed with cold isopropanol (30 kg)
  14. customdried at 50° C.

Sources & evidence

ORD record
ord-0fa0c1f574744f849f48d72740391104
Source dataset
uspto-grants-1992_06
Patent number
US05122514

Reaction notes

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