Tert-butyl [(6-chloropyridin-3-yl)methyl][3-hydroxy-3-(5-oxo-3-pyrrolidin-1-yl-2,5-dihydrofuran-2-yl)propyl]carbamate → 4-[(6-chloropyridin-3-yl)methyl]-7-hydroxy-5,6,7,7a-tetrahydrofuro-[3,2-b]pyridin-2(4H)-one

HRID 552907Notes

Reaction equation

HRID 552907 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:17][CH2:18][CH:19]([OH:31])[CH:20]2[C:24](N3CCCC3)=[CH:23][C:22](=[O:30])[O:21]2)C(=O)OC(C)(C)C)=[CH:4][CH:3]=1>ClCCl.FC(F)(F)C(O)=O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:17][CH2:18][CH:19]([OH:31])[CH:20]3[O:21][C:22](=[O:30])[CH:23]=[C:24]23)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 86632443Tert-butyl [(6-chloropyridin-3-yl)methyl][3-hydroxy-3-(5-oxo-3-pyrrolidin-1-yl-2,5-dihydrofuran-2-yl)propyl]carbamate

Product 1

HCID 577798174-[(6-chloropyridin-3-yl)methyl]-7-hydroxy-5,6,7,7a-tetrahydrofuro-[3,2-b]pyridin-2(4H)-oneYield 6.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
100 °C

Procedure

At room temperature, 176 mg (0.35 mmol) of tert-butyl [(6-chloropyridin-3-yl)methyl][3-hydroxy-3-(5-oxo-3-pyrrolidin-1-yl-2,5-dihydrofuran-2-yl)propyl]carbamate (cf. V-2) are stirred in a mixture of 7 ml of dichloromethane and 3.5 ml of trifluoroacetic acid for one hour. After concentration under reduced pressure, 10.5 ml of acetic acid are added to the residue, and the mixture is stirred at 100° C. for two hours. After concentration under reduced pressure, the residue is 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 (99:1 to 80:20). This gives (a) 6 mg (6% of theory) of 4-[(6-chloropyridin-3-yl)methyl]-7-hydroxy-5,6,7,7a-tetrahydrofuro-[3,2-b]pyridin-2(4H)-one as a mixture of diastereomers and (b) 30 mg (32% of theory) of 4-[(6-chloropyridin-3-yl)methyl]-5,6-dihydrofuro[3,2-b]pyridin-2(4H)-one.

Workup

  1. concentrationAfter concentration under reduced pressure, 10.5 ml of acetic acid
  2. additionare added to the residue
  3. concentrationAfter concentration under reduced pressure
  4. customthe residue is purified by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record
ord-603751359240450689fdb87d91023f06
Source dataset
uspto-grants-2011_05
Patent number
US07951951B2

Reaction notes

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