Pyrrolidine → 5-Fluoro-2-(3-pyrrolidin-1-ylmethyl-benzo[d]isoxazol-6-yloxy)-benzonitrile

HRID 1897459Notes

Reaction equation

HRID 1897459 reaction equation
Br[CH2:2][C:3]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=3[C:15]#[N:16])=[CH:11][C:6]=2[O:5][N:4]=1.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1>ClCCl>[F:21][C:18]1[CH:19]=[CH:20][C:13]([O:12][C:10]2[CH:9]=[CH:8][C:7]3[C:3]([CH2:2][N:22]4[CH2:26][CH2:25][CH2:24][CH2:23]4)=[N:4][O:5][C:6]=3[CH:11]=2)=[C:14]([CH:17]=1)[C:15]#[N:16]

Participants

4

Reactant 2

HCID 31268PyrrolidineHCID 674092672-(3-Bromomethylbenzo[d]isoxazol-6-yloxy)-5-fluorobenzonitrile

Product 1

HCID 674101705-Fluoro-2-(3-pyrrolidin-1-ylmethyl-benzo[d]isoxazol-6-yloxy)-benzonitrileYield 94%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(3-Bromomethylbenzo[d]isoxazol-6-yloxy)-5-fluorobenzonitrile (4v) (0.295 g, 0.850 mmol) was dissolved in dichloromethane and pyrrolidine was added dropwise (0.18 g, 2.5 mmol). After 2 hours, the reaction was concentrated and partitioned between NaHCO3 (15 mL) and EtOAc (30 mL). The aqueous layer was back extracted with EtOAc and the organic fractions were combined, washed with brine and dried (MgSO4) to provide compound (5v) (0.27 g, 94%) which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J=8.6 Hz, 1H), 7.42 (d, J=6.3 Hz, 1H), 7.30-7.26 (m, 1H), 7.11 (s, 1H), 7.07-7.02 (m, 2H), 4.02 (s, 2H), 2.62 (s, 4H), 1.82 (s, 4H); MS (ESI+) m/z 338 (M+H) detected.

Workup

  1. concentrationthe reaction was concentrated
  2. custompartitioned between NaHCO3 (15 mL) and EtOAc (30 mL)
  3. extractionThe aqueous layer was back extracted with EtOAc
  4. washwashed with brine
  5. dry with materialdried (MgSO4)

Sources & evidence

ORD record
ord-cb3330c575fb4d0a959d95f669f791c9
Source dataset
uspto-grants-2013_08
Patent number
US08518983B2

Reaction notes

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