Potassium Hydroxide → HCID 58305287, compound

HRID 1805333Notes

Reaction equation

HRID 1805333 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([C:19]4[N:20]=[CH:21][NH:22][CH:23]=4)[C:11]3=[O:24])[CH2:9]2)=[CH:4][CH:3]=1.C[O:26][C:27](=[O:30])[CH2:28]Br.[OH-].[K+]>CC[N+](CC1C=CC=CC=1)(CC)CC.[Cl-].C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@@:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([C:19]4[N:20]=[CH:21][N:22]([CH2:28][C:27]([OH:30])=[O:26])[CH:23]=4)[C:11]3=[O:24])[CH2:9]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 60984Methyl bromoacetateHCID 178517350HCID 178517350, compound

Product 1

HCID 58305287HCID 58305287, compoundYield 71.7%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of racemic (1S,2R) and (1S,2R)-2-(4-chlorophenyl)-1′-(1 H-imidazol-4-yl)spiro[cyclopropane-1,3′-indolin]-2′-one (0.4 mmol, 134 mg), methyl-bromoacetate (61.2 mg, 0.4 mmol) and 5 mg of TEBA (0.008 mmol) in 2 mL of DCM was added 50% KOH (0.5 mL). The reaction mixture was stirred at room temperature for 14 hours. Then the mixture was concentrated under reduced pressure and acidified to pH˜4. The residue was dissolved in 2 mL of DMF. Purification by preparative HPLC gave the title compound as a white powder (113 mg, 68%). LC/MS m/e calcd. for C21H16ClN3O3: 393, observed (M+H)+: 394.2 1H NMR (400 MHz, DMSO-d6) δppm 2.05-2.16 (m, 1 H) 2.39 (dd, J=7.96, 4.93 Hz, 1 H) 3.20 (t, J=8.72 Hz, 1 H) 4.97 (s, 2 H) 6.18 (d, J=7.07 Hz, 1 H) 6.79 (t, J=7.20 Hz, 1 H) 7.06-7.22 (m, 1 H) 7.38 (s, 4 H) 7.54 (d, J=1.01 Hz, 1 H) 7.69 (d, J=7.83 Hz, 1 H) 7.74 (d, J=1.26 Hz, 1 H). MS calcd. for C21H16ClN3O3 393, obsd. (ESI+) [(M+H)+] 394.3.

Workup

  1. concentrationThen the mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in 2 mL of DMF
  3. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-456793e716ff4ef28b56bef9bafd5f2a
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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