Triethylamine → Methyl 3-(hydroxymethyl)-5-iodobenzoate

HRID 1740283Notes

Reaction equation

HRID 1740283 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([I:14])[CH:13]=1)[C:8](O)=[O:9])=[O:4].C(N(CC)CC)C.ClC(OCC(C)C)=O>O1CCCC1>[OH:9][CH2:8][C:7]1[CH:6]=[C:5]([CH:13]=[C:12]([I:14])[CH:11]=1)[C:3]([O:2][CH3:1])=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 158403913-Iodo-5-(methoxycarbonyl)benzoic acid

Product 1

HCID 21837989Methyl 3-(hydroxymethyl)-5-iodobenzoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-methoxycarbonyl-5-iodobenzoic acid (1 g) in tetrahydrofuran (10 ml) was added at -40° C. to -30° C. triethylamine (0.55 ml) followed by slow addition of isobutyl chloroformate (0.51 ml) under nitrogen atmosphere. The reaction mixture was stirred below -20° C. for 45 minutes. Then, triethylamine hydrochloride was filtered off and washed with cold tetrahydrofuran, and the filtrate was added as quickly as possible to a suspension of sodium borohydride (0.37 g) in tetrahydrofuran-water (8:1, 8 ml) at 0° C. with vigorous stirring. The stirring was continued at ambient temperature for 4 hours, followed by acidification of the solution to pH 5. The tetrahydrofuran was removed under reduced pressure, and the product was extracted with ethyl acetate. The organic layer was washed with water and brine and dried over magnesium sulfate. Ethyl acetate was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (30:1). The fractions containing the desired product were collected and evaporated in vacuo to give methyl 3-hydroxymethyl-5-iodobenzoate.

Workup

  1. filtrationThen, triethylamine hydrochloride was filtered off
  2. washwashed with cold tetrahydrofuran
  3. additionthe filtrate was added as quickly as
  4. additionpossible to a suspension of sodium borohydride (0.37 g) in tetrahydrofuran-water (8:1, 8 ml) at 0° C. with vigorous stirring
  5. waitThe stirring was continued at ambient temperature for 4 hours
  6. customThe tetrahydrofuran was removed under reduced pressure
  7. extractionthe product was extracted with ethyl acetate
  8. washThe organic layer was washed with water and brine
  9. dry with materialdried over magnesium sulfate
  10. customEthyl acetate was removed under reduced pressure
  11. customthe residue was purified by column chromatography on silica gel eluting with a mixture of chloroform and methanol (30:1)
  12. additionThe fractions containing the desired product
  13. customwere collected
  14. customevaporated in vacuo

Sources & evidence

ORD record
ord-17bffa13b8ad4e7fb3bab79383fa086b
Source dataset
uspto-grants-1999_10
Patent number
US05968985

Reaction notes

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