Water → 3-(4-{[2-(Methoxycarbonyl)benzyl]thio}phenyl)propanoic acid

HRID 899879

반응식

HRID 899879 반응식
[SH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:16][C:17]1[CH:26]=[CH:25][CH:24]=[CH:23][C:18]=1[C:19]([O:21][CH3:22])=[O:20].O>C1COCC1>[CH3:22][O:21][C:19]([C:18]1[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=1[CH2:16][S:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][C:10]([OH:12])=[O:11])=[CH:6][CH:7]=1)=[O:20]

참가 물질

6

반응물 4

HCID 962WaterHCID 24758Sodium hydride2회HCID 5797844-Mercaptohydrocinnamic AcidHCID 2734813Methyl 2-(bromomethyl)benzoate

생성물 1

HCID 691205943-(4-{[2-(Methoxycarbonyl)benzyl]thio}phenyl)propanoic acid수율 62.4%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

3-(4-Mercaptophenyl)propanoic acid (2.0 g, 10.97 mmol) was dissolved in dry THF (60 ml) and cooled to 0° C. Sodium hydride (0.64 g, 24.1 mmol) was added. The mixture was stirred for 30 minutes, methyl 2-(bromomethyl)benzoate (2.77 g, 12.07 mmol) dissolved in dry THF (10 ml) was added dropwise. The solution was allowed to warm up to room temperature and was stirred overnight. Dropwise addition of water (10 ml) deactivated the remaining sodium hydride. The solvent was removed by evaporation, and the residue was acidified to pH 3 (HCl 1%). The water phase was washed with EtOAc (3×10 ml). The organic phases was combined, dried (MgSO4) and evaporated. 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 was pooled and the acetonitrile was removed by evaporation. EtOAc (10 ml) was added and the organic phase was washed with two potions of brine and dried (MgSO4). Removing the solvent by evaporation gave 2.26 gram of 3-(4-{[2-(methoxycarbonyl)benzyl]thio}phenyl)propanoic acid (yield 62.3%).

후처리

  1. additionwas added dropwise
  2. temperatureto warm up to room temperature
  3. stirringwas stirred overnight
  4. customThe solvent was removed by evaporation
  5. washThe water phase was washed with EtOAc (3×10 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated
  8. customThe crude was purified by preparative HPLC (
  9. concentrationthe acetonitrile concentration
  10. temperaturewas increased to 100%
  11. 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)
  12. additionThe product containing fractions
  13. customthe acetonitrile was removed by evaporation
  14. additionEtOAc (10 ml) was added
  15. washthe organic phase was washed with two potions of brine
  16. dry with materialdried (MgSO4)
  17. customRemoving the solvent
  18. customby evaporation

출처 및 근거

ORD 기록
ord-e94964de836c4425ae706f602d85f1f9
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07355069B2

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