Carbon tetrabromide → 4-[3-(6-Bromo-hexyl)-2-(ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

HRID 1670067Notes

Reaction equation

HRID 1670067 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20]O)[C:10]=1[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:2].C(Br)(Br)(Br)[Br:31].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][Br:31])[C:10]=1[CH2:22][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:2]

Participants

5

Reactant 3

HCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 575864504-[2-(2-Ethoxycarbonyl-ethyl)-3-(6-hydroxy-hexyl)-phenoxy]-butyric acid ethyl ester

Product 1

HCID 575864914-[3-(6-Bromo-hexyl)-2-(ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl esterYield 87.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
7.5 °C

Procedure

To a solution of 4-[2-(2-ethoxycarbonyl-ethyl)-3-(6-hydroxy-hexyl)-phenoxy]-butyric acid ethyl ester (0.85 mmol, 349 mg) and carbon tetrabromide (1.26 mmol, 423 mg) in dichloromethane (10 mL) was added triphenylphosphine (1.07 mmol, 281 mg) at −0° C. The resulting colorless solution was stirred for 3 h at 5-10° C. Then, the solvent was removed under vacuum and the crude was tried to dissolve in a mixture of ethyl acetate and hexanes (1:3, 50 mL). As a result, a cloudy solution containing some precipitate was formed and the cloudy solution was transferred into a separatory funnel and was washed with a mixture of methanol and water (2:1, 150 mL). The aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL). The combined organic extracts were washed with brine solution (100 mL) and the organic solution was dried over anhydrous magnesium sulfate. Filtration of the drying agent and the removal of the solvent gave a colorless oil which was purified by using a Biotage™ (40M) column chromatography eluting with 10% ethyl acetate in hexanes to obtain the desired 4-[3-(6-bromo-hexyl)-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (350 mg, 87.5%) as a colorless oil: ES(+)-HRMS m/e calculated for C23H35BrO5 (M+Na)+ 493.1560, found 493.1560.

Workup

  1. customThen, the solvent was removed under vacuum
  2. dissolutionto dissolve in a mixture of ethyl acetate and hexanes (1:3, 50 mL)
  3. additionAs a result, a cloudy solution containing some precipitate
  4. customwas formed
  5. customthe cloudy solution was transferred into a separatory funnel
  6. washwas washed with a mixture of methanol and water (2:1, 150 mL)
  7. extractionThe aqueous layer was extracted one more time with ethyl acetate and hexanes (1:3, 50 mL)
  8. washThe combined organic extracts were washed with brine solution (100 mL)
  9. dry with materialthe organic solution was dried over anhydrous magnesium sulfate
  10. filtrationFiltration of the drying agent
  11. customthe removal of the solvent
  12. customgave a colorless oil which
  13. customwas purified
  14. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c049fe1e093e4226be0ad84d0f24846d
Source dataset
uspto-grants-2011_08
Patent number
US07989454B2

Reaction notes

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