Sodium hydride → Ammonium Hydroxide

HRID 550989Notes

Reaction equation

HRID 550989 reaction equation
[OH:1][CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][C:7]3[CH2:24][C@:14]4([C:22]5[C:17](=[N:18][CH:19]=[CH:20][CH:21]=5)[NH:16][C:15]4=[O:23])[CH2:13][C:8]=3[CH:9]=2)[N:4]=1.[H-].[Na+].[CH3:27][Si:28]([CH3:35])([CH3:34])[CH2:29][CH2:30][O:31][CH2:32]Cl>CN(C=O)C>[NH4+:4].[OH-:1].[OH:1][CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:5](=[CH:6][C:7]3[CH2:24][C@:14]4([C:22]5[C:17](=[N:18][CH:19]=[CH:20][CH:21]=5)[N:16]([CH2:32][O:31][CH2:30][CH2:29][Si:28]([CH3:35])([CH3:34])[CH3:27])[C:15]4=[O:23])[CH2:13][C:8]=3[CH:9]=2)[N:4]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 67016575(S)-2-(Hydroxymethyl)-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one2×

Product 2

HCID 14923Ammonium HydroxideHCID 67016509(S)-2-(Hydroxymethyl)-1'-{[2-(trimethylsilyl)ethoxy]methyl}-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3'-pyrrolo[2,3-b]pyridin]-2'(1'H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-2-(hydroxymethyl)-6,8-dihydrospiro[cyclopenta[g]quinoline-7,3′-pyrrolo[2,3-b]pyridin]-2′(1′H)-one (1.67 g, 5.26 mmol, described in Intermediate 11) in DMF (10 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil; 210 mg, 5.26 mmol) and the mixture was stirred for 30 min. 2-(Trimethylsilyl)ethoxymethyl chloride (0.93 mL, 5.26 mmol) was then added dropwise. After 90 min, the reaction was quenched with saturated aqueous NaHCO3 (50 mL) and the mixture was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered, concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:MeOH:NH4OH—100:0:0 to 90:9:1, to give the title compound. MS: m/z=448 (M+1).

Workup

  1. waitAfter 90 min
  2. customthe reaction was quenched with saturated aqueous NaHCO3 (50 mL)
  3. extractionthe mixture was extracted with CH2Cl2 (3×100 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-710f9ceaf23841549f6b64d397be10c7
Source dataset
uspto-grants-2011_05
Patent number
US07947677B2

Reaction notes

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