Phosphate → HCID 22007157, compound

HRID 323790Notes

Reaction equation

HRID 323790 reaction equation
[C:1]([O:4][CH:5]([CH2:18][Cl:19])[C:6]1[CH:11]=[C:10]([S:12](=[O:15])(=[O:14])[NH2:13])[CH:9]=[CH:8][C:7]=1[O:16][CH3:17])(=[O:3])[CH3:2].COC(C)(C)C.P([O-])([O-])([O-])=O.[OH-].[Na+]>C(OCC)(=O)C>[C:1]([O:4][CH:5]([CH2:18][Cl:19])[C:6]1[CH:11]=[C:10]([S:12](=[O:14])(=[O:15])[NH2:13])[CH:9]=[CH:8][C:7]=1[O:16][CH3:17])(=[O:3])[CH3:2].[Cl:19][CH2:18][CH:5]([C:6]1[CH:11]=[C:10]([S:12](=[O:15])(=[O:14])[NH2:13])[CH:9]=[CH:8][C:7]=1[O:16][CH3:17])[OH:4]

Participants

7

Reactant 4

HCID 1061PhosphateHCID 14798Sodium HydroxideHCID 15413tert-Butyl methyl etherHCID 22007157HCID 22007157, compound

Product 2

HCID 22007157HCID 22007157, compoundHCID 22007170HCID 22007170, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

2.86 g (9.3 mmol) of (±)-α-chloromethyl-2-methoxy-5-sulphamoylbenzyl acetate and 110 ml of t-butyl methyl ether are introduced into a 500-ml three-necked flask. The mixture is stirred for 15 minutes, 170 ml of phosphate buffer are then added and the mixture is stirred vigorously until an emulsion is obtained. 0.57 g (20%) of lipase SP 523 is then added and the reaction is monitored at room temperature using a pH-stat (addition of 1M sodium hydroxide) and by HPLC on a chiral column, and the degree of conversion of the ester and the enantiomeric excesses of the ester and of the alcohol are determined. After 45 hours of reaction, when the enantiomeric excesses of the ester and of the alcohol are greater than 95%, the reaction medium is diluted with 800 ml of ethyl acetate, the organic phase is separated and the aqueous phase is re-extracted with 3 times 500 ml of ethyl acetate. The organic phases are combined, dried and concentrated, and the residue is purified by 2 successive flash chromatographic runs on a silica column with a 30:70 mixture of ethyl acetate and cyclohexane. 1.32 g of (−)-α-chloromethyl-2-methoxy-5-sulphamoylbenzyl acetate (ee=99%) and 1.05 g of (+)-α-chloromethyl-2-methoxy-5-sulphamoylbenzenemethanol are obtained.

Workup

  1. stirringthe mixture is stirred vigorously until an emulsion
  2. customis obtained
  3. addition0.57 g (20%) of lipase SP 523 is then added
  4. customis monitored at room temperature
  5. customthe organic phase is separated
  6. extractionthe aqueous phase is re-extracted with 3 times 500 ml of ethyl acetate
  7. customdried
  8. concentrationconcentrated
  9. customthe residue is purified by 2 successive flash
  10. additionwith a 30:70 mixture of ethyl acetate and cyclohexane

Sources & evidence

ORD record
ord-d4e4d45eab9a428cab7d53f89601b296
Source dataset
uspto-grants-2001_04
Patent number
US06214882B1

Reaction notes

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