Sodium hydride → HCID 58573102, compound

HRID 931944Notes

Reaction equation

HRID 931944 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:28])[C@:10]3([C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][CH2:13][C:12](=[O:23])[N:11]3[CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:5]2=[CH:4][CH:3]=1.[H-].[Na+].Cl[CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[C:6]2[N:8]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:9](=[O:28])[C@:10]3([C@@H:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][CH2:13][C:12](=[O:23])[N:11]3[CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 58573759HCID 58573759, compound

Product 1

HCID 58573102HCID 58573102, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (rac) (2′S,3′R)-6-chloro-3′-(3-chlorophenyl)-1′-(cyclopropylmethyl)spiro[indoline-3,2′-piperidine]-2,6′-dione (Example 62, Step H) (114 mg, 0.274 mmol) in DMF (2 mL) at 0° C. was added a dispersion of 60% sodium hydride in mineral oil (10.98 mg, 0.274 mmol) followed by (2-(chloromethoxy)ethyl)trimethylsilane (48.4 μL, 0.274 mmol). The reaction mixture was stirred at 0° C. for 30 min and then warmed to room temperature and stirred at room temperature for 24 h. The reaction mixture was poured into ice water and extracted with EtOAc. The organic layer was washed with 1M LiCl, sat. aq. NaCl solution, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: 0 to 50% EtOAc in hexanes) to give the title compound.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred at room temperature for 24 h
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with 1M LiCl, sat. aq. NaCl solution
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash chromatography on silica gel (eluent: 0 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a22dc3aa1a1246289b112066cbfd765b
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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