n-Butyl lithium → 8-(1-(1-((Tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848558Notes

Reaction equation

HRID 1848558 reaction equation
Br[C:2]1[C:3]([CH3:19])=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7]([O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13])[O:6][CH2:5]2.[Li+].CCC[CH2-].[CH3:25][C:26]([N:30]1[CH2:40][CH2:39][C:33]2([C:37](=[O:38])[NH:36][CH2:35][CH2:34]2)[CH2:32][CH2:31]1)([CH3:29])[CH:27]=[O:28]>O1CCCC1>[Si:12]([O:11][CH:7]1[C:8]2[C:4](=[C:3]([CH3:19])[C:2]([CH:27]([OH:28])[C:26]([N:30]3[CH2:40][CH2:39][C:33]4([C:37](=[O:38])[NH:36][CH2:35][CH2:34]4)[CH2:32][CH2:31]3)([CH3:29])[CH3:25])=[CH:10][CH:9]=2)[CH2:5][O:6]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 61028n-Butyl lithiumHCID 867095372-Methyl-2-(1-oxo-2,8-diazaspiro[4.5]decan-8-yl)propanalHCID 86709540((5-Bromo-4-methyl-1,3-dihydroisobenzofuran-1-yl)oxy)(tert-butyl)dimethylsilan

Product 1

HCID 867095398-(1-(1-((Tert-butyldimethylsilyl)oxy)-4-methyl-1,3-dihydroisobenzofuran-5-yl)-1-hydroxy-2-methylpropan-2-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ((5-bromo-4-methyl-1,3-dihydroisobenzofuran-1-yl)oxy)(tert-butyl)dimethylsilan (3.9 g, 11.36 mmol) in tetrahydrofuran (50 ml) at −78° C. was added N-butyllithium (5.00 ml, 12.50 mmol). After 15 min, 2-methyl-2-(1-oxo-2,8-diazaspiro[4.5]decan-8-yl)propanal (0.892 g, 3.98 mmol) was added in one portion. The resulting solution was stirred at −78° C. for 3.5 h before being quenched by addition of methanol (6 mL) and saturated sodium bicarbonate (100 mL). The mixture was extracted with 30% isopropanol/methylene chloride (3×100 mL). The combined organic phase was dried over sodium sulfate, concentrated and the residue was purified on silica gel using methanol/methylene chloride to give the title compound. LC/MS: (M+1)+: 489.15.

Workup

  1. custombefore being quenched by addition of methanol (6 mL) and saturated sodium bicarbonate (100 mL)
  2. extractionThe mixture was extracted with 30% isopropanol/methylene chloride (3×100 mL)
  3. dry with materialThe combined organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customthe residue was purified on silica gel

Sources & evidence

ORD record
ord-e0a0409b121e48619f15f72f037f4c25
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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