Lithium Hydroxide → 2-{3-[3-(2-Ethyl-5-hydroxy-4-thiazol-2-yl-phenoxy)propoxy]-2-propyl-phenoxy}benzoic acid

HRID 1008310Notes

Reaction equation

HRID 1008310 reaction equation
COC(=O)[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]3[CH:27]=[C:26]([OH:28])[C:25]([C:29]4[S:30][CH:31]=[CH:32][N:33]=4)=[CH:24][C:23]=3[CH2:34][CH3:35])[C:12]=2[CH2:36][CH2:37][CH3:38])[CH:5]=1.[OH-:40].[Li+].CO.[O:44]1[CH2:49]COCC1>>[CH2:34]([C:23]1[CH:24]=[C:25]([C:29]2[S:30][CH:31]=[CH:32][N:33]=2)[C:26]([OH:28])=[CH:27][C:22]=1[O:21][CH2:20][CH2:19][CH2:18][O:17][C:13]1[C:12]([CH2:36][CH2:37][CH3:38])=[C:11]([CH:16]=[CH:15][CH:14]=1)[O:10][C:6]1[CH:5]=[CH:4][CH:9]=[CH:8][C:7]=1[C:49]([OH:44])=[O:40])[CH3:35]

Participants

4

Reactant 3

HCID 3939Lithium HydroxideHCID 21966525Dioxane MethanolHCID 1363883863-[3-(2-Ethyl-5-hydroxy-4-thiazol-2-yl-phenoxy)propoxyl-2-propylphenoxy}benzoic acid methyl ester

Product 1

HCID 1355369512-{3-[3-(2-Ethyl-5-hydroxy-4-thiazol-2-yl-phenoxy)propoxy]-2-propyl-phenoxy}benzoic acidYield 69%

Procedure

2-{3-[3-(2-Ethyl-5-hydroxy-4-thiazol-2-yl-phenoxy)propoxyl-2-propylphenoxy}benzoic acid methyl ester (107 mg, 0.196 mmol) was dissolved in a 1:1 solution of methanol/dioxane (3 mL) and treated with 1 N lithium hydroxide solution (1 mL) at 60° C. for 2 h. The mixture was concentrated in vacuo and the residue diluted with water, washed twice with diethyl ether, and the aqueous layer acidified with 1 N hydrochloric acid. The resulting solution was extracted twice with methylene chloride and the combined organic layers dried (magnesium sulfate), filtered, and concentrated in vacuo. Trituration (hexane) of the residue provided 72 mg (69%) of the title compound as a tan powder. 1H NMR (CDCl3) δ 8.22 (dd, J=8, 2 Hz, 1H), 7.70 (d, J=4 Hz, 1H), 7.41 (dt, J=8, 2 Hz, 1H), 7.35 (s, 1H), 7.18 (m, 3H), 6.82 (d, J=9 Hz, 1H), 6.69 (d, J=9 Hz, 1H), 6.62 (d, J=9 Hz, 1H), 6.55 (s, 1H), 4.22 (t, J=6 Hz, 2H), 4.21 (t, J=6 Hz, 2H), 2.57 (m, 4H), 2.35 (quintet, J=6 Hz, 2H), 1.49 (hextet, J=8 Hz, 2H), 1.18 (t, J=7 Hz, 3H}, 0.86 (t, J=7 Hz, 3H); MS ES+ m/e 534 (p+1); IR (KBr, cm−1) 2957, 1695, 1599, 1457. Anal. Calcd for C30H31NO6S: C, 67.52; H, 5.B6; N, 2.62. Found: C, 67.44; H, 5.95; N, 2.55.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue diluted with water
  3. washwashed twice with diethyl ether
  4. extractionThe resulting solution was extracted twice with methylene chloride
  5. dry with materialthe combined organic layers dried (magnesium sulfate)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-575e32b18aa749cc9a5b7dacad04c149
Source dataset
uspto-grants-2004_09
Patent number
US06797723B1

Reaction notes

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