Water → HCID 67208725, compound

HRID 579180Notes

Reaction equation

HRID 579180 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:29]#[C:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[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@@:12]([CH2:23][CH:24]([OH:27])CO)([CH3:22])[C:11]1=[O:28])=[O:4].O.I([O-])(=O)(=O)=O.[Na+].[BH4-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:29]#[C:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[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@@:12]([CH2:23][CH2:24][OH:27])([CH3:22])[C:11]1=[O:28])=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 4311764Sodium borohydrideHCID 23667635Sodium periodate2×HCID 66684550HCID 66684550, compound

Product 1

HCID 67208725HCID 67208725, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3-[(2R,5R)-5-Cyclohexyl-2-(2,3-dihydroxy-propyl)-2-methyl-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester from Example 7 Step 3 was dissolved in 4 ml THF, and 3.7 mL solution was taken out for the reaction. To the stirred solution was added THF (2.3 mL), water (2.0 mL), and then sodium periodate (0.28 g, 1.31 mmol, 1.6 equiv) at 0° C. The resulting solution was stirred at room temperature for 30 minutes. And then at 0° C. another portion of sodium periodate (0.09 g, 0.44 mmol, 0.5 equiv) was added to the mixture and stirred for another 30 minutes at room temperature. The reaction was quenched by adding brine solution (0.5 mL) and EtOAc (10 mL). The organic layer was separated, dried (over Na2SO4) and concentrated. The residue was dissolved in ethanol (6.0 mL) and to the resulting solution at 0° C. was added sodium borohydride (0.27 g, 7.0 mmol, 8.8 equiv). The mixture was stirred at 0° C. for 15 minutes after which the reaction was quenched by adding water (2.0 mL) and EtOAc (10 mL). The organic layer was separated, dried (over Na2SO4) and concentrated to give product 128 mg (yield 35%). The crude product was continued to the next step with no further purification. MS: 462 [M−H+].

Workup

  1. customat 0° C
  2. stirringstirred for another 30 minutes at room temperature
  3. customThe reaction was quenched
  4. additionby adding brine solution (0.5 mL) and EtOAc (10 mL)
  5. customThe organic layer was separated
  6. dry with materialdried (over Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in ethanol (6.0 mL) and to the resulting solution at 0° C.
  9. stirringThe mixture was stirred at 0° C. for 15 minutes after which the reaction
  10. customwas quenched
  11. additionby adding water (2.0 mL) and EtOAc (10 mL)
  12. customThe organic layer was separated
  13. dry with materialdried (over Na2SO4)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-7655254e8e734c22a427262e85ecbb93
Source dataset
uspto-grants-2015_05
Patent number
US09040690B2

Reaction notes

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