Lithium hydroxide, monohydrate → HCID 58305282, compound

HRID 1805355Notes

Reaction equation

HRID 1805355 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([N:11]2[C:19]3[C:14](=[CH:15][C:16]([F:20])=[CH:17][CH:18]=3)[C@@:13]3([CH2:22][C@@:21]3([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=3)[CH:23]([CH3:25])[CH3:24])[C:12]2=[O:33])[CH:10]=1)[C:5]([O-:7])=[O:6].O[Li].[OH2:36]>CO.O>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([C@:21]2([CH:23]([CH3:24])[CH3:25])[C@:13]3([C:14]4[C:19](=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=4)[N:11]([C:9]4[CH:8]=[C:4]([CH:3]=[C:2]([N:11]5[CH2:9][CH2:8][O:36][C:12]5=[O:33])[CH:10]=4)[C:5]([OH:7])=[O:6])[C:12]3=[O:33])[CH2:22]2)=[CH:27][CH:28]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86654395HCID 86654395, compound

Product 1

HCID 58305282HCID 58305282, compoundYield 108%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of (1R,2R) and (1S,2S)-3-bromo-5-(2-(4-chlorophenyl)-5′-fluoro-2-isopropyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)benzoate (27.4 mg) in methanol (2 mL) and water (1 mL) was added LiOH.H2O (18 mg, 0.4 mmol) in one portion. The mixture was stirred at room temperature for 3 hours until the starting material was consumed. The mixture was concentrated under reduced pressure and acidified to pH˜3. The precipitates was collected by filtration and dissolved in 2 mL of DMF. Purification by preparative HPLC gave the title compound as white solid (15 mg). LC/MS m/e calcd. for C29H24ClFN2O5 534, observed (M+H)+: 545.7. 1H NMR (400 MHz, MeOD-d4) δppm 0.89 (dd, J=20.34, 6.69 Hz, 6 H) 2.21-2.28 (m, 2 H) 2.89-3.01 (m, 1H) 4.22 (t, J=8.08 Hz, 2 H) 4.55 (t, J=8.08 Hz, 2 H) 5.28 (dd, J=8.84, 2.27 Hz, 1 H) 6.65 (dd, J=8.34, 1.77 Hz, 1 H) 6.80-6.89 (m, 2 H) 7.19 (dd, J=8.34, 2.02 Hz, 1 H) 7.45-7.54 (m, 2 H) 7.86 (s, 1 H) 8.09 (s, 1 H) 8.22 (s, 1 H).

Workup

  1. customwas consumed
  2. concentrationThe mixture was concentrated under reduced pressure
  3. filtrationThe precipitates was collected by filtration
  4. dissolutiondissolved in 2 mL of DMF
  5. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-0ca2a3402f184476a9c9244b6785239c
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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