Acetone Cyanohydrin → HCID 11602883, compound

HRID 899436Notes

Reaction equation

HRID 899436 reaction equation
[F:1][C:2]1([F:30])[CH2:29][CH:5]2[CH:6]([C:19]3[CH:24]=[CH:23][C:22]([O:25]COC)=[CH:21][CH:20]=3)[O:7][C:8]3[C:9]([CH3:18])=[CH:10][C:11]([O:14]COC)=[CH:12][C:13]=3[CH:4]2[CH2:3]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)(O)[C:52]#[N:53].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[F:30][C:2]1([F:1])[CH2:29][CH:5]2[CH:6]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[O:7][C:8]3[C:9]([CH2:18][C:52]#[N:53])=[CH:10][C:11]([OH:14])=[CH:12][C:13]=3[CH:4]2[CH2:3]1

Participants

6

Reactant 4

HCID 6406Acetone CyanohydrinHCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 67076779HCID 67076779, compound

Product 1

HCID 11602883HCID 11602883, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of preparation 20 (58 mg, 0.132 mmol) and triphenyl phosphine (175 mg, 0.67 mmol) and acetone cyanohydrin (0.125 mL, 1.37 mmol) in 1 mL of THF at 0° C. add dropwise via syringe diisopropylazodicarboxylate (0.13 mL, 0.66 mmol). Let the solution warm slowly to room temperature overnight. Concentrate the solution, adsorb the material to silica gel, and purify by silica gel flash chromatography (10 g, 0-30% A/B, A=EtOAc, B=10% CH2Cl2 in hexanes). Dissolve the material in 2 mL of THF and add 1 mL of 5 M aqueous HCl. Stir the solution overnight. Dilute the solution with EtOAc and a little methanol for solubility, wash with saturated aqueous sodium bicarbonate, brine, dry over Na2SO4, filter and concentrate. Adsorb the material to silica gel and purify by silica gel flash chromatography (4 g, 10-60% A/B, A=10% methanol in EtOAc, B=hexanes) to afford example 10. HRMS calc. for C20H17F2NNaO3: 380.1074; found: 380.1060 (M+Na).

Workup

  1. concentrationConcentrate the solution
  2. custompurify by silica gel flash chromatography (10 g, 0-30% A/B
  3. dissolutionDissolve the material in 2 mL of THF
  4. additionadd 1 mL of 5 M aqueous HCl
  5. additionDilute the solution with EtOAc
  6. washa little methanol for solubility, wash with saturated aqueous sodium bicarbonate, brine
  7. dry with materialdry over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate
  10. custompurify by silica gel flash chromatography (4 g, 10-60% A/B
  11. customA=10% methanol in EtOAc, B=hexanes) to afford example 10

Sources & evidence

ORD record
ord-ea5057f7743a4abe85fb3821b7a28632
Source dataset
uspto-grants-2008_04
Patent number
US07354951B2

Reaction notes

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