Lithium hydroxide, monohydrate → 4-(4-(Dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

HRID 529012Notes

Reaction equation

HRID 529012 reaction equation
[CH2:1]([N:5]([CH2:45][CH2:46][CH2:47][CH3:48])[C:6]([C:8]1[N:9]=[C:10]([C:21]2[CH:30]=[CH:29][C:24]([C:25]([O:27]C)=[O:26])=[CH:23][C:22]=2[C:31]([N:33]2[C@H:42]([CH2:43][OH:44])[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34]2)=[O:32])[N:11]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4].C1COCC1.CO.O.O[Li].O>O>[CH2:45]([N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:8]1[N:9]=[C:10]([C:21]2[CH:30]=[CH:29][C:24]([C:25]([OH:27])=[O:26])=[CH:23][C:22]=2[C:31]([N:33]2[C@H:42]([CH2:43][OH:44])[CH2:41][C:40]3[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=3)[CH2:34]2)=[O:32])[N:11]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:12]=1)=[O:7])[CH2:46][CH2:47][CH3:48]

Participants

5

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 21892291Methanol tetrahydrofuran waterHCID 71086503Methyl 4-(4-(dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Product 1

HCID 710863334-(4-(Dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acidYield 92.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of methyl 4-(4-(dibutylcarbamoyl)-1-phenethyl-1H-imidazol-2-yl)-3-((S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (110 mg, 0.169 mmol) in mixed solvents (2:2:1 THF/MeOH/H2O, 5.0 mL) was treated with LiOH H2O (21 mg, 0.507 mmol) at 0° C. The reaction mixture was allowed to warm to room temperature over 30 min and stirring was continued for 1 h. The reaction mixture was concentrated to give crude product, which was diluted with water and extracted with MTBE. The aqueous layer was neutralized with 0.5N HCl and extracted with DCM (3×). The combined organic layers were dried over Na2SO4 and concentrated in vacuo to give the title product (100 mg, 91%), which was used without purification. MS(ESI+) m/z 637.2 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customto give crude product, which
  3. extractionextracted with MTBE
  4. extractionextracted with DCM (3×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8ca1b21425d04b1ea9ec290132529d65
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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