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

HRID 528998Notes

Reaction equation

HRID 528998 reaction equation
[CH2:1]([N:5]([CH2:36][CH2:37][CH2:38][CH3:39])[C:6]([C:8]1[N:9]=[C:10]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][C:15]=2[C:24]([N:26]2[CH2:35][CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[N:11]([CH3:13])[CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4].C1COCC1.CO.O.O[Li].O>O>[CH2:1]([N:5]([CH2:36][CH2:37][CH2:38][CH3:39])[C:6]([C:8]1[N:9]=[C:10]([C:14]2[CH:23]=[CH:22][C:17]([C:18]([OH:20])=[O:19])=[CH:16][C:15]=2[C:24]([N:26]2[CH2:35][CH2:34][C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH2:27]2)=[O:25])[N:11]([CH3:13])[CH:12]=1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 21892291Methanol tetrahydrofuran waterHCID 71062400Methyl 4-(4-(dibutylcarbamoyl)-1-methyl-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

Product 1

HCID 710623034-(4-(Dibutylcarbamoyl)-1-methyl-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acidYield 88.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of methyl 4-(4-(dibutylcarbamoyl)-1-methyl-1H-imidazol-2-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (65 mg, 0.12 mmol) in mixed solvents (THF/MeOH/H2O; 2:2:1; 5 mL) was added LiOH H2O (15 mg, 0.36 mmol) at 0° C. The reaction mixture was allowed 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 layer was dried over Na2SO4 and concentrated in vacuo to give the title compound (55 mg, 87%). 1H NMR (CD3OD, 1:1 mixture of amide rotamers) δ 8.28 (dd, J=8.0, 1.6 Hz, 1H), 8.14 (s, 1H), 7.77 (dd, J=13.6, 8.4 Hz, 1H), 7.63 (s, 0.5H), 7.51 (s, 0.5H), 7.23-7.13 (m, 3.5H), 6.95 (d, J=9.2 Hz, 0.5H), 4.79 (s, 1H), 4.48 (s, 1H), 3.77 (s, 1.5H), 3.68 (s, 1.5H), 3.58-3.01 (m, 6H), 2.88-2.80 (m, 2H), 1.60-1.40 (m, 2H), 1.39-1.20 (m, 4H), 1.19-1.00 (m, 2H), 0.99-0.90 (m, 3H), 0.85-0.75 (m, 3H); MS(ESI+) m/z 517.4 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-0888a8da8e8e42d689d8dabb1ecdae4a
Source dataset
uspto-grants-2016_05
Patent number
US09346795B2

Reaction notes

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