Bromine → HCID 57779807, compound

HRID 552895Notes

Reaction equation

HRID 552895 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]([CH2:16][CH2:17][OH:18])[C:10]2[CH2:14][O:13][C:12](=[O:15])[CH:11]=2)=[CH:4][CH:3]=1.C([Li])CCC.BrBr.[Cl-].[NH4+]>O1CCCC1.CCCCCC>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:16][CH2:17][O:18][CH:14]3[O:13][C:12](=[O:15])[CH:11]=[C:10]23)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 24408BromineHCID 25517Ammonium ChlorideHCID 57779825HCID 57779825, compoundHCID 178418339Butyllithium

Product 1

HCID 57779807HCID 57779807, compoundYield 33.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

At −78° C., a solution of 202 mg (0.75 mmol) of 4-[[(6-chloropyridin-3-yl)methyl](2-hydroxyethyl)-amino]furan-2(5H)-one (II-1) in 7 ml of tetrahydrofuran, also cooled to −78° C., is added to a mixture of 0.6 ml (1.50 mmol) of a 2.5M solution of n-butyllithium in hexane and 3 ml of tetrahydrofuran. After 20 minutes of stirring at −78° C., 39 μl (0.75 mmol) of bromine are added a little at a time, and stirring at −78° C. is continued for a further 30 min. After addition of saturated aqueous ammonium chloride solution, the mixture is warmed to room temperature and extracted with ethyl acetate. The combined organic phase is dried over magnesium sulphate and concentrated under reduced pressure. Purification of the residue 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) gives 67 mg (32% of theory) of 1-[(6-chloropyridin-3-yl)methyl]-2,3-dihydro-1H-furo[2,3-b][1,4]oxazin-6(4aH)-one.

Workup

  1. stirringstirring at −78° C.
  2. waitis continued for a further 30 min
  3. temperaturethe mixture is warmed to room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic phase is dried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customPurification of the residue by column chromatography on silica gel (silica gel 60, Merck, particle size: 0.04 to 0.063 mm)

Sources & evidence

ORD record
ord-981020692b9048a0a8c148a8f64d9828
Source dataset
uspto-grants-2011_05
Patent number
US07951951B2

Reaction notes

Loading…