EDTA disodium salt → HCID 87403365, compound

HRID 1716453Notes

Reaction equation

HRID 1716453 reaction equation
[CH3:1][S:2]([O:5][C@H:6]([C@@H:19]1[CH:23]=[CH:22][CH2:21][O:20]1)[CH2:7][NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])(=[O:4])=[O:3].C(N(CC([O-])=O)CC(O)=O)CN(CC([O-])=O)CC(O)=[O:29].[Na+].[Na+].FC(F)(F)C(C)=O.C(=O)(O)[O-].[Na+].OOS([O-])=O.[K+]>C(#N)C.O>[CH3:1][S:2]([O:5][C@H:6]([C@H:19]1[O:20][CH2:21][C@H:22]2[C@@H:23]1[O:29]2)[CH2:7][NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])(=[O:3])=[O:4]

Participants

8

Reactant 5

HCID 8759EDTA disodium saltHCID 9871Methyl trifluoromethyl ketoneHCID 516892Sodium BicarbonateHCID 23707502Potassium hydroxy sulfiteHCID 86632766HCID 86632766, compound

Product 1

HCID 87403365HCID 87403365, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of mesylate (51) (439 mg, 1.29 mmol) in acetonitrile (7 mL) and aqueous Na2.EDTA (7 mL, 0.4 mmol solution) at 0° C. was added 1,1,1-trifluoroacetone (1.38 mL, 15.4 mmol). To this solution was added in portions a mixture of sodium bicarbonate (0.907 g, 10.8 mmol) and OXONE® (2.45 g, 3.99 mmol) over a period of 80 minutes. The mixture was stirred for 30 minutes then diluted with water (10 mL) and the product extracted into dichloromethane (1×10 mL and 2×20 mL). The combined organic layers were washed with brine (30 mL) then dried (MgSO4), filtered and reduced in vacuo. Flash chromatography over silica, eluting with ethyl acetate:heptane mixtures 10:90 to 50:50 gave (in order of elution) anti-(52) (271 mg, 59%) and syn-epoxide (71 mg, 15%) as colourless oils. Data for anti-(52); TLC (Rf=0.41, EtOAc:heptane 3:2), analytical HPLC single main peak, Rt=13.556 min., HPLC-MS 358.2 [M+H]+, 380.2 [M+Na]+, 737.3 [2M+Na]+; [□]D12.5−28.8° (c=1.910, CHCl3); δH (500 MHz, CDCl3) 2.99 (3H, s, OSO2CH3), 3.47 and 3.50 (1H total, each brt, J=6.24 Hz, CH2NH), 3.60 and 3.63 (1H total, each brt, 5.63 respectively, CH2NH), 3.86-3.90 (3H, m, OCH2CHCH), 3.98 (1H, d, J=10.27 Hz, OCH2CH), 4.17 (1H, d, J=2.70 Hz, OCHCHOMs), 4.83-4.87 (1H, m, CHOMs), 5.08-5.14 (2H m, CH2Ph), 5.23 (1H, brs, NH), 7.30-7.36 (5H, m, aromatic CH); δC (125 MHz, CDCl3) 38.570 (OSO2CH3), 42.217 (CH2NHCbz), 56.231 and 57.062 (OCH2CHCH), 67.176 (CH2Ph), 68.353 (OCH2CH), 77.063 (OCHCHOMs), 79.435 (CHOMs), 128.209, 128.343 and 128.587 (aromatic CH), 136.089 (Cbz quaternary), 156.528 (Cbz C═O). Data for syn-epoxide; TLC (Rf=0.29, EtOAc:heptane 3:2), analytical HPLC main peak, Rt=13.639 min., HPLC-MS 358.1 [M+H]+, 737.2 [2M+Na]+; [□]D12.5−9.2° (c=3.543, CHCl3); δH (500 MHz, CDCl3) 3.04 (3H, s, OSO2CH3), 3.60-3.80 (2H, m, CH2NH), 3.72 (1H, d, J=10.54 Hz, OCH2CHCH), 3.79 (1H, d, J=2.90 Hz, epoxide CH), 3.96 (1H, d, J=2.84 Hz, epoxide CH), 3.99 (1H, d, J=7.36 Hz, OCHCHOMs) 4.06 (1H, d, J=10.68 Hz, OCH2CHCH), 4.78 (1H, dt, 4.25 Hz, CHOMs), 5.07-5.14 (2H, m, CH2Ph), 5.29 (1H, brs, NH), 7.29-7.37 (5H, m, aromatic CH); δC (125 MHz, CDCl3) 38.234 (OSO2CH3), 42.241 (CH2NHCbz), 55.571 and 56.081 (OCH2CHCH), 67.047 (CH2Ph), 67.852 (OCH2CH), 76.662 (OCHCHOMs), 80.615 (CHOMs), 128.023, 128.195 and 128.531 (aromatic CH), 136.212 (Cbz quaternary), 156.653 (Cbz C═O).

Workup

  1. additionTo this solution was added in portions
  2. extractionthe product extracted into dichloromethane (1×10 mL and 2×20 mL)
  3. washThe combined organic layers were washed with brine (30 mL)
  4. dry with materialthen dried (MgSO4)
  5. filtrationfiltered
  6. washFlash chromatography over silica, eluting with ethyl acetate
  7. customgave
  8. wash(in order of elution) anti-(52) (271 mg, 59%)
  9. custom5−28.8° (c=1.910, CHCl3)
  10. custom5−9.2° (c=3.543, CHCl3)

Sources & evidence

ORD record
ord-2a43d21dbc4e4c5f82acb71cdda83fbc
Source dataset
uspto-grants-2010_09
Patent number
US07803803B2

Reaction notes

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