Imidazole → 4-Iodomethyl-2-(2-methylphenyl)benzoic acid, methyl ester

HRID 1532873Notes

Reaction equation

HRID 1532873 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:25]I.O[CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH:30]=1>CCOCC.CCCCCC.CCOCC.C(#N)C>[I:25][CH2:28][C:29]1[CH:38]=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[C:31]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[CH:30]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 113912084-Hydroxymethyl-2-(2-methylphenyl)benzoic acid methyl ester

Product 1

HCID 206999164-Iodomethyl-2-(2-methylphenyl)benzoic acid, methyl esterYield 71.5%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolvent2×HCID 6342AcetonitrileSolventHCID 21584099Diethylether hexaneSolvent

Procedure

Triphenylphosphine (5.16 g), and imidazole (1.34 g) were dissolved in 3:1 ether:acetonitrile (80 mL), and the reaction was cooled to 0° C. Iodine (5.0 g) was added with vigorous stirring, and the reaction was warmed to ambient temperature. After 1 h, the reaction was recooled to 0° C. and 4-hydroxymethyl-2-(2-methylphenyl)benzoic acid, methyl ester (example 1178C, 4.6 g) was added as a solution in ether (20 mL). After 4 h at ambient temperature, the reaction was diluted with hexane/ether (1:1, 200 mL) and filtered. The filtrate was washed with a dilute solution of Na2SO3 until colorless, then with water (2×50 mL). The organic extracts were washed with brine (20 mL), dried (MgSO4), filtered and concentrated. The residue was purified by silica gel chromatography eluting with 10% EtOAc/hexane to give a light yellow oil (4.7 g) which slowly crystalizes in the freezer. 1H NMR (300 MHz, CDCl3) δ2.06 (s, 3H), 3.60 (s, 3H), 4.45 (ABq, JAB=9.7 Hz, ΔνAB=6.7 Hz, 2H), 7.03 (brd, J=6.6 Hz, 1H), 7.17-7.29 (m, 4H), 7.41 (dd, J=8.1, 1.6 Hz, 1H), 7.90 (d, J=8.1 Hz, 1H)). MS(CI/NH3) m/e: (M+NH4)+ 384.

Workup

  1. customwas recooled to 0° C.
  2. waitAfter 4 h at ambient temperature
  3. filtrationfiltered
  4. washThe filtrate was washed with a dilute solution of Na2SO3 until colorless, then with water (2×50 mL)
  5. washThe organic extracts were washed with brine (20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 10% EtOAc/hexane

Sources & evidence

ORD record
ord-0905582a254747e7a159c1b396707d65
Source dataset
uspto-grants-2001_03
Patent number
US06204293B1

Reaction notes

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