Lithium hydroxide, monohydrate → (5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetic acid

HRID 734423Notes

Reaction equation

HRID 734423 reaction equation
[CH2:1]([C:4]1[CH:28]=[C:27]([C:29]2[S:30][C:31]3[CH2:37][CH2:36][CH2:35][CH2:34][C:32]=3[N:33]=2)[CH:26]=[CH:25][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]([O:23]C)=[O:22])[CH:15]=[CH:14]2)[CH2:2][CH3:3].O[Li].O>C1COCC1.O>[CH2:1]([C:4]1[CH:28]=[C:27]([C:29]2[S:30][C:31]3[CH2:37][CH2:36][CH2:35][CH2:34][C:32]=3[N:33]=2)[CH:26]=[CH:25][C:5]=1[O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:20][C:21]([OH:23])=[O:22])[CH:15]=[CH:14]2)[CH2:2][CH3:3]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57845400methyl (5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetate

Product 1

HCID 11341093(5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetic acidYield 99.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl (5-{3-[2-propyl-4-(4,5,6,7-tetrahydro-1,3-benzothiazol-2-yl)phenoxy]propoxy}-1H-indol-1-yl)acetate (Example 55, 145 mg, 0.28 mmol) in THF (4.8 mL), was added LiOH.H2O (39 mg, 0.84 mmol) in water (1.6 mL), and the mixture was stirred for 12 h at rt. The solvents were evaporated and a small volume of water was added to the residue. The pH of the mixture was adjusted to 3 with 1N HCl. The aqueous layer was extracted with ethyl acetate. The combined organic layers were dried, filtered, and concentrated to give 140 mg (99%) of the product as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, 1H), 7.25-7.15 (m, 3H), 7.10 (d, 1H), 6.92 (dd, 1H), 6.45 (d, 1H), 6.20 (d, 1H), 4.85 (s, 2H), 4.40-4.32 (m, 2H), 4.32-4.22 (m, 2H), 2.90-2.80 (br, 2H), 2.80-2.70 (br, 2H), 2.50-2.40 (m, 2H), 2.25-2.05 (m, 2H), 1.95-1.75 (br, 4H), 1.60-1.40 (m, 2H), 0.90 (t, 3H). LC/MS m/z 505.2 (M+H)+, RT 3.88 min.

Workup

  1. customThe solvents were evaporated
  2. additiona small volume of water was added to the residue
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. customThe combined organic layers were dried
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-6e0d36e284ad457886ffb4c22a599ea8
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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