Tributyltin Chloride → N-(4-methoxybenzyl)-1-(5-(tributylstannyl)thiazol-2-yl)cyclobutanamine

HRID 2362714Notes

Reaction equation

HRID 2362714 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][C:11]1[CH:27]=[CH:26][C:14]([CH2:15][NH:16][C:17]2([C:21]3[S:22][CH:23]=[CH:24][N:25]=3)[CH2:20][CH2:19][CH2:18]2)=[CH:13][CH:12]=1.[CH2:28]([Sn:32](Cl)([CH2:37][CH2:38][CH2:39][CH3:40])[CH2:33][CH2:34][CH2:35][CH3:36])[CH2:29][CH2:30][CH3:31]>O1CCCC1>[CH3:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH2:15][NH:16][C:17]2([C:21]3[S:22][C:23]([Sn:32]([CH2:33][CH2:34][CH2:35][CH3:36])([CH2:37][CH2:38][CH2:39][CH3:40])[CH2:28][CH2:29][CH2:30][CH3:31])=[CH:24][N:25]=3)[CH2:20][CH2:19][CH2:18]2)=[CH:26][CH:27]=1

Participants

5

Reactant 3

HCID 15096Tributyltin ChlorideHCID 2724682Lithium diisopropylamideHCID 58513757N-(4-methoxybenzyl)-1-(thiazol-2-yl)cyclobutanamine

Product 1

HCID 67003559N-(4-methoxybenzyl)-1-(5-(tributylstannyl)thiazol-2-yl)cyclobutanamine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A freshly prepared solution of lithium diisopropylamide (12.83 mmol) in anhydrous tetrahydrofuran (15 mL) at −10° C. was added dropwise via cannula over 20 minutes to a −78° C. solution of N-(4-methoxybenzyl)-1-(thiazol-2-yl)cyclobutanamine (1.6 g, 5.83 mmol) (Example 112B) in anhydrous tetrahydrofuran (45 mL). The temperature was maintained below −70° C. during the addition, and after the addition, the reaction was stirred 45 minutes at −78° C. Tributyltin chloride (1.89 mL, 7.00 mmol) was then added dropwise. The cold bath was removed, and the reaction was allowed to warm to ambient temperature over 20 minutes. The reaction was quenched with saturated ammonium chloride, and the product was extracted with ethyl acetate. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with a gradient of 10% to 20% ethyl acetate in hexanes, to provide the title compound. MS ESI(+) m/z 565.1 [M+H]+.

Workup

  1. temperatureThe temperature was maintained below −70° C. during the addition
  2. additionafter the addition
  3. customThe cold bath was removed
  4. temperatureto warm to ambient temperature over 20 minutes
  5. customThe reaction was quenched with saturated ammonium chloride
  6. extractionthe product was extracted with ethyl acetate
  7. washThe combined extracts were washed with water and brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by flash chromatography on silica gel
  12. washeluting with a gradient of 10% to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-487ebd5aed1e479ab8500ff55fb0cf2c
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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