Methyl iodide → HCID 19819809, compound

HRID 1031144Notes

Reaction equation

HRID 1031144 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([OH:9])=[O:8].[CH2:10]([Li])CCC.CI.[CH2:17](Br)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1.CCCCCC>[CH3:10][C:6]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:7]([OH:9])=[O:8]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 7498Benzyl BromideHCID 159702-Thiopheneacetic acidHCID 178418339Butyllithium2×

Product 1

HCID 19819809HCID 19819809, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of 2-thiopheneacetic acid (30 g, 0.211 mol) in THF (300 mL) was added dropwise n-butyl lithium (275 mL of a 1.6M solution in hexane). The ice-bath was removed and the reaction was stirred for 1 hour. The reaction mixture was again cooled to 0° C. and hexamethylphosphoramide (34.5 mL) was added dropwise. After 45 minutes a solution of methyl iodide (13.1 mL, 0.211 mol) in THF (75 mL) was added dropwise. The reaction was stirred to room temperature for 45 minutes, recooled to 0° C., n-butyl lithium (1 eq) was added and after 45 minutes a solution of benzyl bromide (36 g, 0.211 mol) in THF (75 mL) was added. After stirring for 3 days the reaction was quenched with 1N.HCl (400 mL). The reaction mixture was partitioned between ethyl acetate and aqueous HCl and the ethyl acetate layer was separated, washed with water, and dried (MgSO4). Concentration of the ethyl acetate afforded an oil which was chromatographed on silica gel and eluted with 40% ethyl acetate/hexanes to give the title product as an oil (63 g).

Workup

  1. customThe ice-bath was removed
  2. additionhexamethylphosphoramide (34.5 mL) was added dropwise
  3. stirringThe reaction was stirred to room temperature for 45 minutes
  4. customrecooled to 0° C.
  5. additionwas added
  6. stirringAfter stirring for 3 days the reaction
  7. customwas quenched with 1N
  8. customThe reaction mixture was partitioned between ethyl acetate and aqueous HCl
  9. customthe ethyl acetate layer was separated
  10. washwashed with water
  11. dry with materialdried (MgSO4)
  12. customConcentration of the ethyl acetate afforded an oil which
  13. customwas chromatographed on silica gel
  14. washeluted with 40% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e627fb6ed95b4ec38784d6e10776f770
Source dataset
uspto-grants-1992_04
Patent number
US05109017

Reaction notes

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