Sodium hydride → (1R,2S)-2-(4-chlorophenyl)-1'-((tetrahydro-2 H-pyran-4-yl)methyl)spiro[cyclopropane-1,3'-indolin]-2'-one

HRID 1805321Notes

Reaction equation

HRID 1805321 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:10]3([C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[NH:12][C:11]3=[O:19])[CH2:9]2)=[CH:4][CH:3]=1.ClC1C=[CH:25][C:24]([C@H:27]2[C@@:29]3(C4C(=CC=CC=4)N[C:30]3=[O:38])[CH2:28]2)=CC=1.[H-].[Na+].BrCC1CCOCC1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][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]([CH2:28][CH:27]4[CH2:29][CH2:30][O:38][CH2:25][CH2:24]4)[C:11]3=[O:19])[CH2:9]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 27732864-(Bromomethyl)oxaneHCID 58305306(1R,2S)-2-(4-chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-oneHCID 672320902-(4-Chlorophenyl)spiro[cyclopropane-1,3'-indolin]-2'-one

Product 1

HCID 53244943(1R,2S)-2-(4-chlorophenyl)-1'-((tetrahydro-2 H-pyran-4-yl)methyl)spiro[cyclopropane-1,3'-indolin]-2'-oneYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Racemic (1S,2R)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one and (1R,2S)-2-(4-chlorophenyl)spiro[cyclopropane-1,3′-indolin]-2′-one (270 mg, 1.0 mmol, 1.0 equiv.) were added to a stirred solution of sodium hydride (60%, 60 mg, 1.5 mmol) in 5 mL of DMF under argon atmosphere at 0° C. After stirring for 1 hour, 4-bromomethyl-tetrahydropyran (215 mg, 1.2 mmol) was added. The reaction mixture was stirred for 14 hours at room temperature. The crude product was purified by HPLC to give the title compound as a white solid (258 mg, 70%). LC/MS m/e calcd. for C22H22ClNO2: 367, observed (M+H)+: 368.2 1H NMR (400 MHz, MeOD-d4) δppm 1.39-1.55 (m, 2 H) 1.65 (dd, J=13.14, 1.77 Hz, 2 H) 2.11-2.25 (m, 3 H) 3.22 (t, J=8.46 Hz, 1 H) 3.37-3.47 (m, 2 H) 3.79 (d, J=7.33 Hz, 2 H) 3.94-4.04 (m, 2 H) 6.09 (d, J=7.58 Hz, 1 H) 6.76 (t, J=7.58 Hz, 1 H) 7.11 (d, J=7.83 Hz, 1 H) 7.17-7.25 (m, 3 H) 7.33 (d, J=8.34 Hz, 2 H). MS calcd. For C22H22ClNO2 367, obsd. (ESI+) [(M+H)+] 368.

Workup

  1. stirringThe reaction mixture was stirred for 14 hours at room temperature
  2. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-0cc18b52a186493a843a0a1711b0a8c8
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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