Dichloromethane → HCID 59619308, compound

HRID 1367452Notes

Reaction equation

HRID 1367452 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[CH2:8][C@H:7]1[C:12]([O:14]CC)=[O:13])=[O:5])[CH3:2].[Mg].[OH-].[Na+].ClCCl>O1CCN(CCS(O)(=O)=O)CC1>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[CH2:8][C@H:7]1[C:12]([OH:14])=[O:13])=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 5462224MagnesiumHCID 26967534HCID 26967534, compound

Product 1

HCID 59619308HCID 59619308, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 781654-Morpholineethanesulfonic acidSolvent

Procedure

60.44 g of rac-trans-4-oxo-cyclopentane-1,2-dicarboxylic acid diethyl ester (prepared according to E. Lee-Ruff et al., J. Org. Chem. 59, 2114, 1994 or J. Mittendorf et al., Synthesis, 136, 2003) was emulsified under vigorous stirring in 1.16 L 5 mM 2-morpholinoethanesulfonic acid, 50 mM magnesium acetetate buffer pH 6.2. 1.94 ml CALB L (liquid enzyme formulation from Novozymes, Denmark) was added and the pH kept constant at 6.2 under vigorous stirring by the automated addition (pH-stat) of 1.0 M NaOH-solution. After reaching 45% conversion (ca. 42 h reaction time; enantiomeric excess of formed acid still >95% according to GC in process control) 1.0 L dichloromethane was added. The aqueous phase was washed with 3×1.5 L dichloromethane, set to pH 3.0 using 85% phosphoric acid and extracted with 4×1.0 L ethyl acetate. The combined ethyl acetate phases were dried over sodium sulfate, evaporated and dried under high vacuum overnight to give 24.40 g of the title compound as white crystals: MS: 199.1 (M−H); >99% GC; [α]589 (20° C.)=−101.2° (c 1.0; EtOH); chiral GC: 95% ee [BGB-176, 30 m×0.25 mm; H2; 100° C. to 200° C. with 2° C./min].

Workup

  1. addition1.94 ml CALB L (liquid enzyme formulation from Novozymes, Denmark) was added
  2. customca. 42 h reaction time
  3. additionwas added
  4. washThe aqueous phase was washed with 3×1.5 L dichloromethane
  5. extractionextracted with 4×1.0 L ethyl acetate
  6. dry with materialThe combined ethyl acetate phases were dried over sodium sulfate
  7. customevaporated
  8. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-15d6378efb77438a81228059696298eb
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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