Water → HCID 86684774, compound

HRID 579207Notes

Reaction equation

HRID 579207 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=C)[C:11]1=[O:25])=[O:4].C[N+]1([O-])CC[O:36]CC1.O.I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.[Os](=O)(=O)(=O)=O>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=[O:36])[C:11]1=[O:25])=[O:4]

Participants

7

Reactant 4

HCID 962WaterHCID 82029Methyl morpholine oxideHCID 23667635Sodium periodate2×HCID 666842053-((2R,5R)-2-Allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester

Product 1

HCID 86684774HCID 86684774, compoundYield 66.4%

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 180AcetoneSolvent

Procedure

To a solution of 3-((2R,5R)-2-allyl-5-cyclohexyl-3-oxo-morpholin-4-yl)-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (3.15 g, 7.10 mmol, 1.0 equiv) in acetone (40 mL) at 0° C. was added N-methylmorpholine oxide (2.51 g, 21.30 mmol, 3.0 equiv), water (14 mL) and osmium tetroxide (3.60 g, 2.5% wt in THF, 0.36 mmol, 0.05 equiv). The mixture was stirred at room temperature for 60 minutes. Acetone was removed under vacuum and the residue was partitioned between EtOAc (80 mL) and brine (15 mL). The phases were separated and the organic layer was dried (over Na2SO4) and concentrated. To the residue was added THF (40 mL) and water (14 mL). At 0° C., sodium periodate (2.28 g, 10.65 mmol, 1.5 equiv) was added to the mixture and the mixture was stirred at room temperature for 30 minutes. After cooled at 0° C., another portion of sodium periodate (0.76 g, 3.55 mmol, 0.5 equiv) was added. The mixture was stirred at room temperature for another 30 minutes. Volatile solvent was removed under vacuum and the residue was partitioned between EtOAc (100 mL) and brine (10 mL). The organic layer was separated, dried (over Na2SO4) and concentrated. The residue was purified by silica gel column chromatography (EtOAc/Heptane, 25% to 50%) to give product (2.1 g, 66%). MS: 446.3 [M−H+].

Workup

  1. customAcetone was removed under vacuum
  2. customthe residue was partitioned between EtOAc (80 mL) and brine (15 mL)
  3. customThe phases were separated
  4. dry with materialthe organic layer was dried (over Na2SO4)
  5. concentrationconcentrated
  6. additionTo the residue was added THF (40 mL) and water (14 mL)
  7. stirringthe mixture was stirred at room temperature for 30 minutes
  8. temperatureAfter cooled at 0° C.
  9. stirringThe mixture was stirred at room temperature for another 30 minutes
  10. customVolatile solvent was removed under vacuum
  11. customthe residue was partitioned between EtOAc (100 mL) and brine (10 mL)
  12. customThe organic layer was separated
  13. dry with materialdried (over Na2SO4)
  14. concentrationconcentrated
  15. customThe residue was purified by silica gel column chromatography (EtOAc/Heptane, 25% to 50%)

Sources & evidence

ORD record
ord-1264e4d258aa40d4afdc5dadfb8e90e5
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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