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

HRID 1008630Notes

Reaction equation

HRID 1008630 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

100 mg of 4-{2-[1-Benzhydryl-2-(2-carboxy-ethyl)-5-chloro-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester (0.0002 M, 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).

Workup

  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
  5. additionVol. 22, pg.4723, 1981) was 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)

Sources & evidence

ORD record
ord-64fcd6d15c8b4fa7bae659df1edd13fb
Source dataset
uspto-grants-2004_09
Patent number
US06797708B2

Reaction notes

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