Lithium hydroxide, monohydrate → (1R,2S)-1-(2-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylic acid

HRID 1805336Notes

Reaction equation

HRID 1805336 reaction equation
C[O:2][C:3]([C:5]1[N:6]=[CH:7][N:8]([CH2:10][CH2:11][N:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C@@:14]3([CH2:22][C@@H:21]3[C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C:13]2=[O:30])[CH:9]=1)=[O:4].COC(C1N=CN(CCN2C3C(=CC=CC=3)[C@]3(C[C@H]3C3C=CC(Cl)=CC=3)C2=O)C=1)=O.O[Li].O>CO.O>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([C@H:21]2[C@@:14]3([C:15]4[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=4)[N:12]([CH2:11][CH2:10][N:8]4[CH:9]=[C:5]([C:3]([OH:4])=[O:2])[N:6]=[CH:7]4)[C:13]3=[O:30])[CH2:22]2)=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 168937Lithium hydroxide, monohydrateHCID 58305314(1R,2S)-methyl-1-(2-(2-(4-chlorophenyl)-2'-oxospiro [cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylateHCID 58305337methyl-1-(2-((1S,2R)-2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylate

Product 1

HCID 58305404(1R,2S)-1-(2-(2-(4-chlorophenyl)-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylic acidYield 88%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of methyl-1-(2-((1S,2R)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)ethyl)-1H-imidazole-4-carboxylate and methyl-1-(2-((1R,2S)-2-(4-chlorophenyl)-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)ethyl)-1H-imidazole-4-carboxylate (0.07 mmol) 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 residue was dissolved in 2 mL of DMF. Purification by preparative HPLC gave the title compound as a white powder (26 mg, 88%). LC/MS m/e calcd. for C22H18ClN3O3: 407, observed (M+H)+: 408.8 1H NMR (400 MHz, MeOD) δppm 2.10 (dd, J=28.17, 8.46 Hz, 2 H) 3.10 (s, 1 H) 4.31 (s, 2 H) 4.86 (s, 2 H) 6.05 (d, J=7.33 Hz, 1 H) 6.75 (s, 1 H) 6.90-7.45 (m, 6 H) 7.86 (s, 1 H) 8.27 (s, 1 H).

Workup

  1. customwas consumed
  2. concentrationThe mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in 2 mL of DMF
  4. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-920075abd302470b99116f37d05cb663
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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