N-bromobutanimide → 4-(5-Bromo-7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidin-4-ol

HRID 1025493Notes

Reaction equation

HRID 1025493 reaction equation
Cl.[F:2][C:3]1[C:11]2[O:10][CH:9]([C:12]3([OH:18])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.C1C(=O)N([Br:26])C(=O)C1>CO.C(Cl)Cl>[Br:26][C:5]1[CH:4]=[C:3]([F:2])[C:11]2[O:10][CH:9]([C:12]3([OH:18])[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]3)[CH2:8][C:7]=2[CH:6]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 674689424-(7-Fluoro-2,3-dihydrobenzofuran-2-yl)piperidin-4-ol hydrochloride

Product 1

HCID 674689374-(5-Bromo-7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidin-4-olYield 40.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(7-fluoro-2,3-dihydrobenzofuran-2-yl)piperidin-4-ol hydrochloride (380 mg, 1.388 mmol) in MeOH (11.1 mL) at 0° C. was added NBS (235 mg, 1.319 mmol) in one portion. Upon completion of addition, the reaction mixture was stirred at room temperature for 3 hours, and then quenched with aqueous Na2H2S2O5 (10%, 5 mL). The solvent was removed under reduced pressure to yield a residue. The residue was diluted with CH2Cl2 (5 mL), washed with aqueous NaOH (1 N, 3 mL) and brine (3 mL). The organic layer was separated, dried (K2CO3), filtered, and concentrated to afford Compound 1G as a white solid (0.168 g, 38% yield). LC/MS (m/z)=317 (M+H)+.

Workup

  1. additionUpon completion of addition
  2. customquenched with aqueous Na2H2S2O5 (10%, 5 mL)
  3. customThe solvent was removed under reduced pressure
  4. customto yield a residue
  5. washwashed with aqueous NaOH (1 N, 3 mL) and brine (3 mL)
  6. customThe organic layer was separated
  7. dry with materialdried (K2CO3)
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-18c05298bfea4b6dbf18b8ecf8289032
Source dataset
uspto-grants-2014_05
Patent number
US08729084B2

Reaction notes

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