Piperidine → 1-(Benzofuran-5-YL)piperidine

HRID 2075149Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.[NH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[O:9]1[C:5]2[CH:4]=[CH:3][C:2]([N:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)=[CH:10][C:6]=2[CH:7]=[CH:8]1

Participants

Conditions

Temperature: 120 °C

Procedure

5-bromobenzofuran (2 g, 10 mmol), piperidine (1.2 mL, 12 mmol), Pd(dppf)Cl2 (245 mg, 0.3 mmol), dppf (250 mg, 0.45 mmol) and sodium tert-butoxide (1.44 g, 15 mmol) was mixed in toluene (10 mL). The mixture was purged with N2 gas for 3-5 min and heated at 120° C. for 30 min under microwave irradiation (Personal Chemistry Emrys™ Optimizer microwave reactor). Upon completion of the reaction, the reaction mixture was directly loaded on silica gel column and purified on ISCO system (<2% EtOAc in hexanes) to give 0.539 g desired product (27% yield): ESI-MS: 202.3 (M+H)+, 1H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.40 (d, 1H), 7.15 (s, 1H), 7.00 (d, 1H), 6.65 (s, 1H), 3.10 (m, 4H), 1.70 (m, 4H), 1.48 (m, 2H). Note: the title compound appeared to be very volatile. The evaporation of solvent should be carried out very carefully.

Workup

customThe mixture was purged with N2 gas for 3-5 min
customUpon completion of the reaction
custompurified on ISCO system (<2% EtOAc in hexanes)

Sources & evidence

ORD record: ord-f80241dc9ca442a094695bddf2007e6c
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919519B2

Reaction notes

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