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

HRID 2237110Notes

Reaction equation

HRID 2237110 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 (0.0002M, 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).

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. 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)

Sources & evidence

ORD record
ord-440cc8d5321044b5827649b883c16cb8
Source dataset
uspto-grants-2010_05
Patent number
US07713964B2

Reaction notes

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