Imidazole → 4-(2-Iodoethyl)-1-[2-methyl-5-(methyloxy)-4-nitrophenyl]piperidine

HRID 419617Notes

Reaction equation

HRID 419617 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[C:5]([O:11][CH3:12])=[CH:4][C:3]=1[N:13]1[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20]O)[CH2:15][CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:46]I>C1COCC1>[I:46][CH2:20][CH2:19][CH:16]1[CH2:17][CH2:18][N:13]([C:3]2[CH:4]=[C:5]([O:11][CH3:12])[C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=2[CH3:1])[CH2:14][CH2:15]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 594527382-{1-[2-Methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}ethanol

Product 1

HCID 594527714-(2-Iodoethyl)-1-[2-methyl-5-(methyloxy)-4-nitrophenyl]piperidineYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To 2-{1-[2-methyl-5-(methyloxy)-4-nitrophenyl]-4-piperidinyl}ethanol (32.6 g, 111 mmol), triphenylphosphine (32.0 g, 122 mmol), and imidazole (8.29 g, 122 mmol) in THF (554 mL) was added iodine (30.9 g, 122 mmol) in one portion, slowly due to observable exotherm. The reaction mixture was filtered through Celite® and washed with DCM. Purification by flash chromatography provided the crude title compound which was washed with saturated Na2SO3 to remove any residual iodine. The aqueous layer was back extracted with DCM. The combined organic layers were dried (MgSO4), filtered, and rotovapped down to give the title compound of step G (40.6 g, 100 mmol, 91% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J=0.5 Hz, 1H), 6.68 (s, 1H), 3.89 (s, 3H), 3.33 (t, J=7.5 Hz, 2H), 3.26 (d, J=12.4 Hz, 2H), 2.63-2.74 (m, 2H), 2.17 (s, 3H), 1.78 (q, J=7.1 Hz, 4H), 1.46-1.61 (m, J=7.2, 7.2, 7.1, 3.8 Hz, 1H), 1.30 (qd, J=12.0, 3.6 Hz, 2H).

Workup

  1. filtrationThe reaction mixture was filtered through Celite®
  2. washwashed with DCM
  3. customPurification by flash chromatography
  4. customprovided the crude title compound which
  5. washwas washed with saturated Na2SO3
  6. customto remove any residual iodine
  7. extractionThe aqueous layer was back extracted with DCM
  8. dry with materialThe combined organic layers were dried (MgSO4)
  9. filtrationfiltered

Sources & evidence

ORD record
ord-0ca0ec3f61a64123a72284cf16caaa3f
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…