Water → 1-Methyl (1S,2R)-4-cyclohexene-1,2-dicarboxylate

HRID 2266935Notes

Reaction equation

HRID 2266935 reaction equation
O.OP([O-])(O)=O.[K+].[OH-].[Na+].[CH3:10][O:11][C:12]([C@@H:14]1[C@H:19]([C:20]([O:22]C)=[O:21])[CH2:18][CH:17]=[CH:16][CH2:15]1)=[O:13]>CC(C)=O.C(OCC)(=O)C.CCCCCC>[CH3:10][O:11][C:12]([C@@H:14]1[C@H:19]([C:20]([OH:22])=[O:21])[CH2:18][CH:17]=[CH:16][CH2:15]1)=[O:13]

Participants

8

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 516951Monobasic potassium phosphate2×HCID 10867283Dimethyl cis-1,2,3,6-tetrahydrophthalate2×

Product 1

HCID 53259071-Methyl (1S,2R)-4-cyclohexene-1,2-dicarboxylateYield 91%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

(1R, 6S)-6-Methoxycarbonyl-3-cyclohexene-1-carboxylic acid (2-3) was prepared following the procedure of Ohno and co-workers4, that had been successfully applied by Appella et al.3 of the Gellman group. Precaution was taken to make sure all glassware was clean. All glassware was washed in acid bath and rinsed twice with Millipore water. To Millipore water (2.6 L) was added KH2PO4 (61.79 g, 454 mmol) and the pH of the resulting solution adjusted to 8 by adding a prepared solution of 2.5 M NaOH and using a pH meter calibrated at pH 4 and pH 10. The diester 2-2 (45 g, 227 mmol) was dissolved in reagent grade acetone (131 mL) and this solution added to the aqueous KH2PO4 solution. Pig liver esterase (10.5 mL, 48189 units) was added, and the resulting solution was stirred for 24 hours. The reaction was monitored by TLC (1:1 hexane:ethyl acetate, Rf (2-2)=0.67, Rf(2-3)=0.24). After ascertaining that reaction was complete, the enzyme was filtered off through celite in a fritted glass funnel. The resulting solution was then acidified with 1M HCl to a pH about 2 and then extracted three times with ethyl acetate (1200 mL total). The organic extracts were dried over MgSO4, concentrated, and dried under vacuum overnight to afford 38 g (91%) of 2-3 as a thick yellow oil: 1H NMR (300 MHz, CDCl3): δ 11.24 (br s, 1H, OH), 5.68 (m, 2H, HC═CH), 3.70 (s, 3H, OCH3), 3.07 (m, 2H, CHCOOCH3 and CHCOOH), 2.62-2.54 (m, 2H, CH2CHCOOCH3 or CH2CHCOOH), 2.41-2.32 (m, 2H, CH2CHCOOCH3 or CH2CHCOOH); 13C NMR (75 MHz, CDCl3): δ 179.6 (C), 173.5 (C), 125.0 (CH), 124.8 (CH), 51.7 (CH3), 39.4 (CH), 39.2 (CH), 25.5 (CH2), 25.3 (CH2); MS-ESI m/z 207.1 [M+Na]+.

Workup

  1. custom(1R, 6S)-6-Methoxycarbonyl-3-cyclohexene-1-carboxylic acid (2-3) was prepared
  2. washAll glassware was washed in acid bath
  3. washrinsed twice with Millipore water
  4. additionPig liver esterase (10.5 mL, 48189 units) was added
  5. customAfter ascertaining that reaction
  6. filtrationthe enzyme was filtered off through celite in a fritted glass funnel
  7. extractionextracted three times with ethyl acetate (1200 mL total)
  8. dry with materialThe organic extracts were dried over MgSO4
  9. concentrationconcentrated
  10. customdried under vacuum overnight

Sources & evidence

ORD record
ord-d25201a265664efbb133b40fb32db5dc
Source dataset
uspto-grants-2010_12
Patent number
US07858737B2

Reaction notes

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