Potassium Hydroxide → 5-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1';3',1'']terphenyl-2'-yloxy]-pentanoic acid

HRID 1743483Notes

Reaction equation

HRID 1743483 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14](=[O:33])[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=[CH:25]3)[CH:11]=[C:10]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[C:9]=2[O:41][CH2:42][CH2:43][CH2:44][CH2:45][C:46]([O:48]CC)=[O:47])[CH:5]=[CH:6][CH:7]=1.[OH-].[K+]>C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([C:14](=[O:33])[NH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH:26]=[CH:25]3)[CH:11]=[C:10]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[C:9]=2[O:41][CH2:42][CH2:43][CH2:44][CH2:45][C:46]([OH:48])=[O:47])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 865836655-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1';3',1'']terphenyl-2'-yloxy]-pentanoic acid, ethyl ester

Product 1

HCID 222376625-[3,3''-Dichloro-5'-(8-indol-1-yl-octylcarbamoyl)-[1,1';3',1'']terphenyl-2'-yloxy]-pentanoic acidYield 63.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 5-[3,3″-Dichloro-5′-(8-indol-1-yl-octylcarbamoyl)-[1,1′;3′,1″]terphenyl-2′-yloxy]-pentanoic acid, ethyl ester (0.409 g, 0.573 mmol) and 1N KOH (1.15 ml) in THF (6 ml) and methanol (3 ml) was stirred under nitrogen. After ˜18 h, the reaction mixture was concentrated in vac. The residue was suspended in water (25 ml) and acidified with 2 N HCl (1.15 ml) then extracted with EtOAc (3×25 ml). The combined organics were washed with water (3×10 ml), brine (2×10 ml), dried over Na2SO4, filtered and the filtrate concentrated in vac and dried. The residue was purified by preparatory plate chromatography (50% EtOAc/Hex) to give the title compound as a light yellow foam (0.249 g, 63%); dec. >50° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.12–1.32 (m, 12H), 1.44–1.53 (m, 2H), 1.67–1.76 (m, 2H), 1.87 (t, J=7.0 Hz, 2H), 3.16–3.27 (m, 4H), 4.12 (t, J=7.0 Hz, 2H), 6.37–6.38 (m, 1H), 6.94–6.99 (m, 1H), 7.06–7.10 (m, 1H), 7.31 (d, J=3.1 Hz, 1H), 7.40–7.52 (m, 6H), 7.56–7.59 (m, 2H), 7.66–7.69 (m, 2H), 7.87 (s, 2H), 8.52 (t, J=5.7 Hz, 1H), 11.85 (s, 1H); IR (KBr) 3400, 2940, 1710, 1630, 1550, 1220 cm−1; mass spectrum [(+)APCI], m/z 685 (M+H)+; Anal. Calcd. for C40H42Cl2N2O4: C, 70.07; H, 6.17; N, 4.09. Found: C, 69.66; H, 6.17; N, 3.85.

Workup

  1. concentrationthe reaction mixture was concentrated in vac
  2. extractionthen extracted with EtOAc (3×25 ml)
  3. washThe combined organics were washed with water (3×10 ml), brine (2×10 ml)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate concentrated in vac
  7. customdried
  8. customThe residue was purified by preparatory plate chromatography (50% EtOAc/Hex)

Sources & evidence

ORD record
ord-e80989ada8144bd2a93f751bdfd1379b
Source dataset
uspto-grants-2006_03
Patent number
US07008636B2

Reaction notes

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