Sodium Chloride → HCID 66918551, compound

HRID 1367454Notes

Reaction equation

HRID 1367454 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]([N:14]1[CH2:19][CH2:18][O:17][CH2:16][CH2:15]1)=[O:13])=[O:5])[CH3:2].C1N(CCS(O)(=O)=O)CCOC1.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.[Cl-].[Mg+2].[Cl-].C1C=[N+]([C@@H]2O[C@H](COP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](OP(O)(O)=O)[C@@H]3O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=C(C(N)=O)C=1.[OH-].[Na+].[Cl-].[Na+]>>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C@H:9]([OH:11])[CH2:8][C@H:7]1[C:12]([N:14]1[CH2:15][CH2:16][O:17][CH2:18][CH2:19]1)=[O:13])=[O:5])[CH3:2]

Participants

8

Reactant 7

HCID 5234Sodium ChlorideHCID 5886NADP nicotinamide-adenine-dinucleotide phosphateHCID 14798Sodium HydroxideHCID 781654-Morpholineethanesulfonic acidHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal2×HCID 5360315Magnesium ChlorideHCID 66918676HCID 66918676, compound2×

Product 1

HCID 66918551HCID 66918551, compound

Procedure

A mixture of 7.77 g of (1R,2R)-2-(morpholine-4-carbonyl)-4-oxo-cyclopentanecarboxylic acid ethyl ester in 148 ml of aqueous buffer (10 mM 2-(N-morpholino)ethanesulfonic acid; 0.5 M D-glucose [2.7 equ.]; 2 mM magnesium chloride) was adjusted to pH 6.5. Under stirring the reduction was started by the addition of the cofactor NADP (779 mg [0.03 equ.]), the cofactor regeneration enzyme-glucose dehydrogenase (77 mg GDH 102 [Codexis]) and the reductase (387 mg KRED-NADP-131 [Codexis]). During the 21 h reaction time the pH was maintained at pH 6.5 by the addition of 31.9 ml 1M NaOH. At this time point the reaction mixture was blended with the use-test previously carried out, in which 1.5 g (1R,2R)-2-(morpholine-4-carbonyl)-4-oxo-cyclopentanecarboxylic acid ethyl ester were reduced under exactly the described conditions. Under stirring the mixture was adjusted to pH 2.8, saturated with 43.6 g sodium chloride and stirred for at least 10 min. after the addition of 17 g filter aid—Dicalite—and 300 ml ethyl acetate. Subsequently the filter aid was removed and the filtrate was adjusted to pH 7.0 prior to extraction. The aqueous phase was extracted twice with 300 ml ethyl acetate. Treatment of the combined organic phases with sodium sulfate, evaporation and drying over night under a high vacuum yielded in 8.73 g of (1R,2R,4R)-4-hydroxy-2-(morpholine-4-carbonyl)-cyclopentanecarboxylic acid ethyl ester as a pale yellow oil. MS: 272.1 (M+H)+; chiral GC: ee 95.2% [BGB-176, 30 m; H2; 2° C./min, 150° C. to 220° C.].

Workup

  1. customDuring the 21 h reaction time the pH
  2. stirringUnder stirring the mixture
  3. stirringstirred for at least 10 min.
  4. additionafter the addition of 17 g
  5. filtrationfilter aid—Dicalite—and 300 ml ethyl acetate
  6. customSubsequently the filter aid was removed
  7. extractionto extraction
  8. extractionThe aqueous phase was extracted twice with 300 ml ethyl acetate
  9. customTreatment of the combined organic phases with sodium sulfate, evaporation
  10. customdrying over night under a high vacuum
  11. customyielded in 8.73 g of (1R,2R,4R)-4-hydroxy-2-(morpholine-4-carbonyl)-cyclopentanecarboxylic acid ethyl ester as a pale yellow oil
  12. customee 95.2% [BGB-176, 30 m; H2; 2° C./min, 150° C. to 220° C.]

Sources & evidence

ORD record
ord-05da2d76c29a4d6c9fe1be1be2c8c509
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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