Triethylamine → HCID 86601924, compound

HRID 2112003Notes

Reaction equation

HRID 2112003 reaction equation
[OH:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][CH2:7][CH2:8][C:9]2[CH:26]=[CH:25][C:12]([O:13][CH2:14][C:15]3[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=3[C:17]([O:19][CH3:20])=[O:18])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>ClCCl>[CH3:36][S:37]([O:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][CH2:7][CH2:8][C:9]2[CH:26]=[CH:25][C:12]([O:13][CH2:14][C:15]3[CH:24]=[CH:23][CH:22]=[CH:21][C:16]=3[C:17]([O:19][CH3:20])=[O:18])=[CH:11][CH:10]=2)=[CH:27][CH:28]=1)(=[O:39])=[O:38]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 68869264HCID 68869264, compound

Product 1

HCID 86601924HCID 86601924, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

Methyl 2-({4-[2-(4-hydroxyphenoxy)ethyl]phenoxy}methyl)benzoate (0.547 g, 1.45 mmol) was dissolved in dichloromethane (10 ml) and the solution was cooled to −20° C. Triethylamine (0.22 g, 2.17 mmol) was added dropwise followed by the dropwise addition of methylsulfonyl chloride (0.18 g, 1.59 mmol). The ice bath was removed and the mixture was stirred overnight at room temperature. Excess of triethylamine was removed by addition of diethyl ether (5 ml) and filtering off the precipitate. The organic phase was washed with three portions of brine (10 ml) and dried (MgSO4). The solvent was removed by evaporation, the crude was purified by preparative HPLC (started with acetonitrile/buffer 60/40 and then the acetonitrile concentration was increased to 100%, the buffer was a mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min)). The product containing fractions were pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two portions of brine and dried (MgSO4). Removing the solvent by evaporation gave 0.317 g of methyl 2-{[4-(2-{4-[(methylsulfonyl)oxy]phenoxy}ethyl)phenoxy]methyl}benzoate (yield 48%).

Workup

  1. customThe ice bath was removed
  2. customExcess of triethylamine was removed by addition of diethyl ether (5 ml)
  3. filtrationfiltering off the precipitate
  4. washThe organic phase was washed with three portions of brine (10 ml)
  5. dry with materialdried (MgSO4)
  6. customThe solvent was removed by evaporation
  7. customthe crude was purified by preparative HPLC (
  8. concentrationthe acetonitrile concentration
  9. temperaturewas increased to 100%
  10. additiona mixture of acetonitrile/water 10/90 and ammonium acetate (0.1 M, column KR-100-7-C8, 50 mm×250 mm, flow 40 ml/min))
  11. additionThe product containing fractions
  12. customthe acetonitrile was removed by evaporation
  13. additionEtOAc (10 ml) was added
  14. washthe organic phase was washed with two portions of brine
  15. dry with materialdried (MgSO4)
  16. customRemoving the solvent
  17. customby evaporation

Sources & evidence

ORD record
ord-e88b60191da047c8a9146850288aff23
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

Loading…