2,2,6,6-Tetramethylpiperidine → 2-(1-(Tert-butyldimethylsilyloxy)cyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethanol

HRID 1696324Notes

Reaction equation

HRID 1696324 reaction equation
CC1(C)CCCC(C)(C)N1.C([Li])CCC.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:19][N:18]=1.[Si:28]([O:35][C:36]1([CH2:40][CH:41]=[O:42])[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]([C:22]2[C:17]([F:16])=[N:18][CH:19]=[C:20]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:21]=2)[OH:42])[CH2:37][CH2:38][CH2:39]1)([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29]

Participants

7

Reactant 4

HCID 130352,2,6,6-TetramethylpiperidineHCID 575158452-Fluoro-5-neopentylpyridineHCID 866140212-(1-((Tert-butyldimethylsilyl)oxy)cyclobutyl)acetaldehydeHCID 178418339Butyllithium

Product 1

HCID 668448842-(1-(Tert-butyldimethylsilyloxy)cyclobutyl)-1-(2-fluoro-5-neopentylpyridin-3-yl)ethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

2,2,6,6-tetramethylpiperidine (13.0 ml, 76.5 mmol) was dissolved in 500 ml THF and cooled to −78° C. Butyllithium (26.8 ml, 67.0 mmol) was added over the period of 10 min and the reaction was allowed to warm up to 0° C. and kept there for 3 min. The mixture was cooled back to −78° C. and a solution of 2-fluoro-5-neopentylpyridine (8.000 g, 47.8 mmol) in 10 ml THF was added over the period of 30 min. The mixture was stirred for 20 min at the same temperature and a solution of 2-(1-(tert-butyldimethylsilyloxy)cyclobutyl)acetaldehyde (19.7 g, 86.1 mmol) in 25 ml THF was added over the period of 20 min. The reaction was stirred for 15 min at the same temperature and hydrolyzed with 200 ml of H2O. The mixture was allowed to warm up to room temp and extracted 2 times with 1 L EtOAc (each). The combined organic extracts were dried over MgSO4 and evaporated. The crude material was used without further purification. MS found 396.2.

Workup

  1. temperatureto warm up to 0° C.
  2. temperatureThe mixture was cooled back to −78° C.
  3. temperatureto warm up to room temp
  4. extractionextracted 2 times with 1 L EtOAc (each)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. customevaporated
  7. customThe crude material was used without further purification

Sources & evidence

ORD record
ord-9b9734a3440347389a78136d2539e3da
Source dataset
uspto-grants-2012_04
Patent number
US08163766B2

Reaction notes

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