1,4-Dibromobutane → HCID 71765182, compound

HRID 2272988Notes

Reaction equation

HRID 2272988 reaction equation
[Mg].[Cl-].[Ce+3].[Cl-].[Cl-].Br[CH2:7][CH2:8][CH2:9][CH2:10]Br.CO[C:14](=[O:32])[C:15]1[CH:20]=[CH:19][C:18]([C:21]2[NH:22][C:23](=[O:31])[C:24]3[N:25]([CH:27]=[C:28]([F:30])[CH:29]=3)[CH:26]=2)=[CH:17][CH:16]=1.C[Mg]Cl>C1COCC1>[F:30][C:28]1[CH:29]=[C:24]2[C:23](=[O:31])[NH:22][C:21]([C:18]3[CH:17]=[CH:16][C:15]([C:14]4([OH:32])[CH2:10][CH2:9][CH2:8][CH2:7]4)=[CH:20][CH:19]=3)=[CH:26][N:25]2[CH:27]=1

Participants

7

Reactant 5

HCID 80561,4-DibromobutaneHCID 24636Cerium(III) chlorideHCID 5462224MagnesiumHCID 89826294HCID 89826294, compound2×HCID 178418332HCID 178418332, compound

Product 1

HCID 71765182HCID 71765182, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
0 °C

Procedure

A 25 ml round-bottom flask is flushed with nitrogen and charged with 6.9 ml dry THF, 134 mg (5.50 mmol) magnesium turnings and 49 mg (0.20 mmol) cerium(III) chloride. Under stirring, the suspension is cooled to 0° C. Then 378 μl (3.20 mmol) 1,4-dibromobutane is added, the suspension is allowed to reach room temperature, stirred for 30 minutes at this temperature and again cooled to 0° C. Then, a solution of 286 mg (1.00 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 2.3 ml THF is added dropwise. The reaction mixture is stirred for 30 minutes at 0° C. and for 1 hour at room temperature. The reaction mixture is quenched with saturated ammonium chloride solution. To a suspension of 5.73 g (20.0 mmol) 4-(7-fluoro-1-oxo-1,2-dihydro-pyrrolo[1,2-a]pyrazin-3-yl)-benzoic acid methyl ester in 85 ml THF are added 5.42 g (22.0 mmol) and the mixture is stirred for 1 h at ambient temperature under nitrogen. Then 30.5 ml (84.0 mmol) of a 20% solution of methylmagnesium chloride in THF is added dropwise and the reaction mixture is stirred for 30 minutes at room temperature. The reaction mixture is partitioned between ethyl acetate and water. The organic phase is dried over sodium sulfate and evaporated. The residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent to afford 7-fluoro-3-[4-(1-hydroxy-cyclopentyl)-phenyl]-2H-pyrrolo[1,2-a]pyrazin-1-one as light orange powder; HPLC/MS 2.37 (B), [M+H] 313; 1H NMR (400 MHz, DMSO-d6) δ [ppm] 10.99 (s, 1H), 7.62 (s, 1H), 7.59 (d, J=8.5 Hz, 2H), 7.54 (d, J=8.5 Hz, 2H), 7.48 (dd, J=3.4, 1.9 Hz, 1H), 6.75 (d, J=1.8 Hz, 1H), 4.85 (s, 1H), 1.92-1.80 (m, 6H), 1.80-1.69 (m, 2H).

Workup

  1. customA 25 ml round-bottom flask is flushed with nitrogen
  2. customto reach room temperature
  3. stirringstirred for 30 minutes at this temperature
  4. temperatureagain cooled to 0° C
  5. stirringThe reaction mixture is stirred for 30 minutes at 0° C. and for 1 hour at room temperature
  6. customThe reaction mixture is quenched with saturated ammonium chloride solution
  7. additionare added 5.42 g (22.0 mmol)
  8. stirringthe mixture is stirred for 1 h at ambient temperature under nitrogen
  9. stirringthe reaction mixture is stirred for 30 minutes at room temperature
  10. customThe reaction mixture is partitioned between ethyl acetate and water
  11. dry with materialThe organic phase is dried over sodium sulfate
  12. customevaporated
  13. customThe residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate as eluent

Sources & evidence

ORD record
ord-08998cb30d3644dc92111a563866e32e
Source dataset
uspto-grants-2015_09
Patent number
US09120805B2

Reaction notes

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