2,2,6,6-Tetramethylpiperidine → N-(2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(3-chloro-6-neopentylpyridazin-4-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 1009154Notes

Reaction equation

HRID 1009154 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[Cl:16][C:17]1[N:18]=[N:19][C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:21][CH:22]=1.[Si:28]([O:35][C:36]1([CH2:40]/[CH:41]=[N:42]/[S:43]([C:45]([CH3:48])([CH3:47])[CH3:46])=[O:44])[CH2:39][CH2:38][CH2:37]1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]>C1COCC1.O>[Si:28]([O:35][C:36]1([CH2:40][CH:41]([NH:42][S:43]([C:45]([CH3:48])([CH3:47])[CH3:46])=[O:44])[C:22]2[CH:21]=[C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[N:19]=[N:18][C:17]=2[Cl:16])[CH2:39][CH2:38][CH2:37]1)([C:31]([CH3:33])([CH3:34])[CH3:32])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 596236793-Chloro-6-neopentylpyridazineHCID 87349347HCID 87349347, compoundHCID 178418339Butyllithium

Product 1

HCID 86645008N-(2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)-1-(3-chloro-6-neopentylpyridazin-4-yl)ethyl)-2-methylpropane-2-sulfinamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

2,2,6,6-Tetramethylpiperidine (0.68 ml, 4.0 mmol) was dissolved in 120 ml THF and 1-butyllithium (1.5 ml, 3.8 mmol) was added at −78° C. drop wise. The mixture was allowed to warm to 0° C. (over a period of 5 min) and kept there for 5 min. The mixture was cooled back to −78° C. and a solution of 3-chloro-6-neopentylpyridazine (0.45 g, 2.4 mmol) in 10 ml of THF was added drop wise. Stirring was continued for 20 min and a solution of (E)-N-(2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)ethylidene)-2-methylpropane-2-sulfinamide (1.450 g, 4.4 mmol) in 5 ml THF was added drop wise. Stirring was continued for 10 min and the mixture was hydrolyzed with H2O. The mixture was extracted with EtOAc (3×300 ml) dried over MgSO4 and evaporated. The crude product was used in the next step without further purification.

Workup

  1. temperatureThe mixture was cooled back to −78° C.
  2. waitwas continued for 20 min
  3. stirringStirring
  4. waitwas continued for 10 min
  5. extractionThe mixture was extracted with EtOAc (3×300 ml)
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe crude product was used in the next step without further purification

Sources & evidence

ORD record
ord-c8f2a4bbee4a4359856559bc1ef34055
Source dataset
uspto-grants-2011_07
Patent number
US07973047B2

Reaction notes

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