Ammonium Chloride → HCID 67403422, compound

HRID 1188192Notes

Reaction equation

HRID 1188192 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[F:9].C([Li])CCCCC.[C:17]([N:24]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25]1)([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[Cl-].[NH4+]>C(OCC)C>[F:9][C:3]1[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=1[C:26]1([OH:29])[CH2:27][CH2:28][N:24]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:25]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 471360Tert-butyl 3-oxopyrrolidine-1-carboxylateHCID 27332601-Bromo-2,3-difluorobenzeneHCID 178506865HCID 178506865, compound

Product 1

HCID 67403422HCID 67403422, compoundYield 66%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 1-bromo-2,3-difluorobenzene (8 g, 41.4 mmol) in dry diethyl ether (100 mL), under nitrogen, was added dropwise at −78° C., n-hexyllithium (2.3 M in hexane, 18 ml, 41.4 mmol). The mixture was stirred for 1 min after which a solution of 1-N-boc-3-pyrrolidone (7.66 g, 41.4 mmol) in dry diethyl ether (50 mL) was added dropwise. The resulting mixture was brought to ambient temperature and stirred for 2 h, aqueous saturated ammonium chloride solution (50 ml) was added and the mixture was extracted with ethylacetate (2×50 ml). The combined organic phase was washed with brine, dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1) to give the title compound (8.12 g, 66%). MS m/z (rel. intensity, 70 eV) 243 (26), 198 (48), 141 (33), 127 (38), 57 (bp).

Workup

  1. additionwas added dropwise
  2. customwas brought to ambient temperature
  3. extractionthe mixture was extracted with ethylacetate (2×50 ml)
  4. washThe combined organic phase was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe crude product was purified by flash column chromatography (ethylacetate/isooctane, 1:9 to 1:1)

Sources & evidence

ORD record
ord-1b1c0a61d121402abfaa35edb1dacc55
Source dataset
uspto-grants-2014_03
Patent number
US08673962B2

Reaction notes

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