Ethyl Acetate → HCID 59468934, compound

HRID 1690097Notes

Reaction equation

HRID 1690097 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][O:9][C:10]1[CH:15]=[CH:14][C:13]([C@@H:16]2[N:20]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@:19](CC=C)([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17]2)=[CH:12][CH:11]=1.C[N+]1([O-])CC[O:39]CC1.CCOC(C)=O.[CH3:49][C:50]([CH3:52])=[O:51].O>>[OH:51][CH:50]([CH2:52][OH:39])[CH2:49][C@@:19]1([C:28]([O:30][CH3:31])=[O:29])[CH2:18][CH2:17][C@H:16]([C:13]2[CH:14]=[CH:15][C:10]([O:9][CH2:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])=[CH:11][CH:12]=2)[N:20]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22]

Participants

5

Reactant 4

HCID 8857Ethyl AcetateHCID 82029Methyl morpholine oxideHCID 18366337Propan-2-one--water (1/1)HCID 59468970HCID 59468970, compound

Product 1

HCID 59468934HCID 59468934, compound

Procedure

The reaction was performed on the two separated batches of 1-(1,1-dimethylethyl) 2-methyl (2R,5R)-5-(4-{[(2-fluorophenyl)methyl]oxy}phenyl)-2-(2-propen-1-yl)-1,2-pyrrolidinedicarboxylate obtained from the previous step (D35). The first batch (119.8 g) was dissolved in a mixture of 10/1 acetone/water (1200 mL). K2OsO4.2H2O (4.7 g) was added followed by NMO (41.4 g) after a few minutes. The mixture was stirred for 7.5 hours. The reaction mixture was treated with EtOAc (1200 mL) and washed with saturated NH4Cl (1200 mL) then with saturated NaHCO3 (1200 mL). The organic layer was filtered through a celite/activated charcoal pad and concentrated to low volume. EtOAc (500 mL) was added and the solution was washed with brine (300 mL) and the organic dried over Na2SO4, and evaporated to dryness, EtOAc (300 mL) was added and filtered through CUNO filter and washed with EtOAc (50 mL). The organic was concentrated to dryness to afford the title compound (135 g). The second batch (179 g) was dissolved in a mixture of 10/1 acetone/water (1800 mL). K2OsO4.2H2O (5.5 g) was added followed by NMO (56.8 g) after a few minutes. The mixture was stirred overnight at room temperature. The reaction mixture was treated with EtOAc (900 mL) and washed with saturated NH4Cl (2×900 mL) then with saturated NaHCO3 (900 mL). The organic layer was filtered through a celite pad and concentrated to low volume to afford the title compound (250 g). 1H NMR (400 MHz, DMSO-d6) δ(ppm): 7.54 (m, 1H); 7.40 (m, 3H); 7.22 (m, 2H); 6.95 (m, 2H); 5.11 (m, 2H); 4.95-4.25 (m, 3H); 3.70 (bm, 3H); 3.50-3.10 (m, 3H); 2.50-1.50 (m, 6H); 1.30-0.95 (4 bs, 9H).

Workup

  1. customobtained from the previous step (D35)
  2. washwashed with saturated NH4Cl (1200 mL)
  3. filtrationThe organic layer was filtered through a celite/activated charcoal pad
  4. concentrationconcentrated to low volume
  5. additionEtOAc (500 mL) was added
  6. washthe solution was washed with brine (300 mL)
  7. dry with materialthe organic dried over Na2SO4
  8. customevaporated to dryness, EtOAc (300 mL)
  9. additionwas added
  10. filtrationfiltered through CUNO
  11. filtrationfilter
  12. washwashed with EtOAc (50 mL)
  13. concentrationThe organic was concentrated to dryness

Sources & evidence

ORD record
ord-23565fb251f14e5b97699e0cae4e9c89
Source dataset
uspto-grants-2012_04
Patent number
US08153623B2

Reaction notes

Loading…