tert-Butanol → 4-[(6-Chloropyridin-3-yl)methyl]-6-hydroxy-6-hydroxymethyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one

HRID 552904Notes

Reaction equation

HRID 552904 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2CC(=C)C[CH:11]3[O:16][C:17](=[O:19])[CH:18]=[C:10]23)=[CH:4][CH:3]=1.C[N+]1([O-])CC[O:24]CC1.[C:28]([OH:32])([CH3:31])([CH3:30])[CH3:29]>O1CCCC1.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:30][C:28]([OH:32])([CH2:31][OH:24])[CH2:29][CH:11]3[O:16][C:17](=[O:19])[CH:18]=[C:10]23)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 6386tert-ButanolHCID 82029Methyl morpholine oxideHCID 577798304-[(6-chloropyridin-3-yl)methyl]-6-methylene-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one

Product 1

HCID 577798284-[(6-Chloropyridin-3-yl)methyl]-6-hydroxy-6-hydroxymethyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one

Reagents, catalysts & solvents 2

HCID 30318Osmium TetroxideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

1.86 g (6.72 mmol) of 4-[(6-chloropyridin-3-yl)methyl]-6-methylene-5,6,7,7a-tetrahydrofuro-[3,2-b]pyridin-2(4H)-one (cf. I-5) are dissolved in 20 ml of tetrahydrofuran, and 5.06 ml (0.40 mmol) of a 2.5% strength solution of osmium tetroxide in tert-butanol and 1.28 g (10.08 mmol) of N-methylmorpholine N-oxide are added successively at 0° C. After 3 hours of stirring at room temperature, the mixture is substantially concentrated under reduced pressure, the residue is taken up in water and the mixture is extracted repeatedly with ethyl acetate. Concentration of the organic phase under reduced pressure gives 1.8 g of crude product (mixture of diastereomers). 200 mg of the crude product (taken into account for the determination of the yield) are purified by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm) using the mobile phase mixture dichloromethane:methanol (95:5 to 90:10). This gives both possible diastereomers of 4-[(6-chloropyridin-3-yl)methyl]-6-hydroxy-6-hydroxymethyl-5,6,7,7a-tetrahydrofuro[3,2-b]pyridin-2(4H)-one: (a) 41 mg (18% of theory) of diastereomer A and (b) 104 mg (47% of theory) of diastereomer B.

Workup

  1. concentrationthe mixture is substantially concentrated under reduced pressure
  2. extractionthe mixture is extracted repeatedly with ethyl acetate
  3. customConcentration of the organic phase under reduced pressure gives 1.8 g of crude product (mixture of diastereomers)
  4. customyield)
  5. customare purified by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record
ord-f4c5e6a1237c4158b0bb06cd8ab50a40
Source dataset
uspto-grants-2011_05
Patent number
US07951951B2

Reaction notes

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