Oxalyl chloride → 4-{2-[1-Benzhydryl-5-chloro-2-(3-hydroxy-propyl)-1H-indol-3-yl]-ethoxy)-benzoic acid methyl ester

HRID 1821494노트

반응식

HRID 1821494 반응식
[CH3:1][O:2][C:3](=[O:41])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][CH2:12][C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([Cl:22])[CH:20]=3)[N:15]([CH:23]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:14]=2[CH2:36][CH2:37][C:38](O)=[O:39])=[CH:6][CH:5]=1.C(Cl)(=O)C(Cl)=O>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:41])[C:4]1[CH:5]=[CH:6][C:7]([O:10][CH2:11][CH2:12][C:13]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([Cl:22])[CH:20]=3)[N:15]([CH:23]([C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:14]=2[CH2:36][CH2:37][CH2:38][OH:39])=[CH:8][CH:9]=1

참가 물질

4

반응물 2

HCID 65578Oxalyl chlorideHCID 161165964-{2-[1-Benzhydryl-2-(2-carboxy-ethyl)-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester

생성물 1

HCID 161159414-{2-[1-Benzhydryl-5-chloro-2-(3-hydroxy-propyl)-1H-indol-3-yl]-ethoxy)-benzoic acid methyl ester수율 83%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

100 mg of 4-{2-[1-Benzhydryl-2-(2-carboxy-ethyl)-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester (0.0002M, 1 eq.) was dissolved in 1.0 ml of anhydrous methylene chloride. To the solution 33.5 mg of oxalyl chloride (0.0003M, 1.5 eq.) was added and the reaction stirred for one hour at room temperature. The reaction was then evaporated to dryness and the residue dissolved in 1.0 mL of anhydrous ethyl ether to which 0.027 mL of TMEDA was added. To this solution 0.35 mL of zinc borohydride solution in ether prepared by the literature method (Tet. Lett. Vol. 22, pg. 4723, 1981) was added. The reaction was stirred for 15 min. at room temperature and quenched with 1.0 mL of water. The reaction was diluted with 10 mL of ethyl ether and the water layer separated, the organic layer was dried over magnesium sulfate, filtered and evaporated to a clear oil. The oil was chromatographed with ethyl acetate/hexanes (1:9) to result in isolation of 4-{2-[1-Benzhydryl-5-chloro-2-(3-hydroxy-propyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester as a white foam (81 mg, 83% yield).

후처리

  1. customThe reaction was then evaporated to dryness
  2. dissolutionthe residue dissolved in 1.0 mL of anhydrous ethyl ether to which 0.027 mL of TMEDA
  3. additionwas added
  4. customTo this solution 0.35 mL of zinc borohydride solution in ether prepared by the literature method (Tet. Lett. Vol. 22, pg. 4723, 1981)
  5. additionwas added
  6. stirringThe reaction was stirred for 15 min. at room temperature
  7. customquenched with 1.0 mL of water
  8. additionThe reaction was diluted with 10 mL of ethyl ether
  9. customthe water layer separated
  10. dry with materialthe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. customevaporated to a clear oil
  13. customThe oil was chromatographed with ethyl acetate/hexanes (1:9)

출처 및 근거

ORD 기록
ord-593d0dad516b4d66a812fee91d77ef2b
출처 데이터셋
uspto-grants-2009_10
특허 번호
US07605156B2

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