Sodium hydride → (1R,2S)-methyl-1-(2-(2-(4-chlorophenyl)-2'-oxospiro [cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylate

HRID 1805335Notes

Reaction equation

HRID 1805335 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][NH:8][CH:9]=1)=[O:4].[H-].[Na+].[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C@@H:19]2[C@:21]3([C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH2:30][C:31]4C=CN=CC=4)[C:22]3=[O:37])[CH2:20]2)=[CH:15][CH:14]=1.BrCCN1C2C(=CC=CC=2)[C@@]2(C[C@@H]2C2C=CC(Cl)=CC=2)C1=O>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]=[CH:7][N:8]([CH2:31][CH2:30][N:23]2[C:24]3[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@:21]3([CH2:20][C@H:19]3[C:16]3[CH:15]=[CH:14][C:13]([Cl:12])=[CH:18][CH:17]=3)[C:22]2=[O:37])[CH:9]=1)=[O:4]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 58305312(1S,2R)-2-(4-chlorophenyl)-1'-(pyridin-4-ylmethyl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 58305388(1S,2R)-1'-(2-bromoethyl)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 178418785HCID 178418785, compound

Product 1

HCID 58305314(1R,2S)-methyl-1-(2-(2-(4-chlorophenyl)-2'-oxospiro [cyclopropane-1,3'-indoline]-1'-yl)ethyl)-1H-imidazole-4-carboxylateYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of methyl-imidazole-4-carboxylate (100 mg, 0.2 mmol) in 1 mL of anhydrous DMF was added NaH (60% disp.) (8.8 mg, 0.22 mmol) at room temperature. The reaction mixture was stirred for 1 hour at that temperature. To the mixture was added a solution of racemic (1R,2S) and (1S,2R)-1′-(2-bromoethyl)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (75.2 mg, 0.2 mmol) in 1 mL of DMF. The reaction was stirred at room temperature for 14 hours and then concentrated under reduced pressure. The residue was dissolved in EtOAc and washed with saturated aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with EtOAc. The organic layers were combined and washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo to give the title compound as white solid (30 mg, 35%). LC/MS m/e calcd. for C23H20ClN3O3: 421, observed (M+H)+: 422.3.

Workup

  1. stirringThe reaction was stirred at room temperature for 14 hours
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in EtOAc
  4. washwashed with saturated aqueous NaHCO3
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washwashed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-755a28dc8f9c4f3784ea5b6cc071fbed
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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