Lithium hydroxide, monohydrate → HCID 89660237, compound

HRID 2274573Notes

Reaction equation

HRID 2274573 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([O:16]CC)=[O:15])=[N:9]2)=[C:4]([C:19]([N:21]2[C@H:30]([CH2:31][OH:32])[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[CH:3]=1.O.[OH-].[Li+]>C1COCC1.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH3:13])=[CH:11][C:10]([C:14]([OH:16])=[O:15])=[N:9]2)=[C:4]([C:19]([N:21]2[C@H:30]([CH2:31][OH:32])[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH2:22]2)=[O:20])[CH:3]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 89660235HCID 89660235, compound

Product 1

HCID 89660237HCID 89660237, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (S)-ethyl 1-(4-bromo-2-(3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-5-methyl-1H-pyrazole-3-carboxylate (50.0 g, 100.6 mmol) in THF (80 mL) and water (20 mL) was added lithium hydroxide monohydrate (21.1 g, 503.0 mmol) followed by stirring at RT for 12 h. The reaction mixture was concentrated invacuo, diluted with water (80 mL) and extracted with diethyl ether (100 mL). The aq. layer was cooled to 0° C., acidified up to pH ˜4 using 3N HCl and extracted with EtOAc (200 mL×2), twice. The combined organic layers were washed with water (200 mL), brine (100 mL), dried over sodium sulphate and concentrated invacuo. The residue was purified on silica gel (100-200 mesh) to afford the title compound as a pale yellow solid, 40 g (crude). Rf=0.10 (30% EtOAc in hexane); 1H NMR (400 MHz, DMSO-d6): δ 12.80-11.80 (m, 1H), 8.15-7.40 (m, 3H), 7.30-6.90 (m, 4H), 6.70-6.30 (m, 1H), 5.10-3.70 (m, 5H), 3.50-2.40 (m, 3H), 2.38-2.10 (m, 3H); ES-MS: m/z 470.5 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated invacuo
  2. additiondiluted with water (80 mL)
  3. extractionextracted with diethyl ether (100 mL)
  4. temperatureThe aq. layer was cooled to 0° C.
  5. extractionextracted with EtOAc (200 mL×2)
  6. washThe combined organic layers were washed with water (200 mL), brine (100 mL)
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated invacuo
  9. customThe residue was purified on silica gel (100-200 mesh)

Sources & evidence

ORD record
ord-4315546e509b47479b2f4b71245bd197
Source dataset
uspto-grants-2015_09
Patent number
US09126980B2

Reaction notes

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