Dimethylformamide → 4-Methyl-5-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)thiazole-2-carbaldehyde

HRID 69097Notes

Reaction equation

HRID 69097 reaction equation
Br[C:2]1[S:3][C:4]([CH2:8][N:9]2[CH2:14][CH2:13][C:12]3([C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH:16]=[CH:15]3)[CH2:11][CH2:10]2)=[C:5]([CH3:7])[N:6]=1.[Li]CCCC.CN([CH:31]=[O:32])C.[NH4+].[Cl-]>C1COCC1.O>[CH3:7][C:5]1[N:6]=[C:2]([CH:31]=[O:32])[S:3][C:4]=1[CH2:8][N:9]1[CH2:14][CH2:13][C:12]2([C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 68194077HCID 68194077, compoundHCID 178418339Butyllithium

Product 1

HCID 866700464-Methyl-5-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)thiazole-2-carbaldehydeYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-45 °C

Procedure

To a solution of 2-bromo-4-methyl-5-(spiro[indene-1,4′-piperidine]-1′-ylmethyl) thiazole (3.8 g, 10.12 mmol) in THF is added n-BuLi (0.713 g, 11.13 mmol) at −78° C. The mixture is warmed to −45° C. and stirred for 30 minutes. DMF (1.5 mL) is added dropwise to the mixture at −78° C. and the mixture is slowly warmed to room temperature and stirred for an hour. The mixture is cooled to −78° C., diluted with water, followed by NH4Cl solution. The mixture is extracted with ethyl acetate, dried over Na2SO4, and evaporated to dryness to give the title compound (2.8 g, 85%). ESI/MS m/z 325 (M+H)+.

Workup

  1. temperaturethe mixture is slowly warmed to room temperature
  2. stirringstirred for an hour
  3. temperatureThe mixture is cooled to −78° C.
  4. extractionThe mixture is extracted with ethyl acetate
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness

Sources & evidence

ORD record
ord-bac1dabb63e0444fa9c1d0ab5209ca9e
Source dataset
uspto-grants-2014_09
Patent number
US08822486B2

Reaction notes

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