Nitrogen → 5-(((Tert-butyldimethylsilyl)oxy)methyl)thiazole-2-carbaldehyde

HRID 82828Notes

Reaction equation

HRID 82828 reaction equation
N#N.Br[C:4]1[S:5][C:6]([CH2:9][O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[CH:7][N:8]=1.[Li]CCCC.CN([CH:26]=[O:27])C.[NH4+].[Cl-]>CCOCC.CCCCCC>[Si:11]([O:10][CH2:9][C:6]1[S:5][C:4]([CH:26]=[O:27])=[N:8][CH:7]=1)([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12]

Participants

8

Reactant 5

HCID 947NitrogenHCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 66821250HCID 66821250, compoundHCID 178418339Butyllithium

Product 1

HCID 867627995-(((Tert-butyldimethylsilyl)oxy)methyl)thiazole-2-carbaldehydeYield 89.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of 2-bromo-5-(((tert-butyldimethylsilyl)oxy)methyl)thiazole (WO 2009/077990, p. 92) (2.0 g, 6.49 mmol) in Et2O (14.0 mL) was treated dropwise at −70° C. with n-BuLi (4.25 mL of a 1.6M solution in hexane, 6.81 mmol). The resulting mixture was stirred for 30 min at −70° C. DMF (0.80 mL, 10.38 mmol) was then added and the resulting mixture was stirred for 20 min at −70° C. Sat. aq. NH4Cl was added, the org. layer was extracted with EA (3×20 mL) and the combined org. layers were dried over MgSO4, filtered and the solvent was removed under reduced pressure to give 1.50 g of 5-(((tert-butyldimethylsilyl)oxy)methyl)thiazole-2-carbaldehyde as a yellow oil: TLC: rf (9:1 hept-EA)=0.31. LC-MS-conditions 07: tR=1.00 min, [M+H]+=257.93. A solution of this material in MeOH (10 mL) was treated at 0° C. with NaBH4 (286 mg, 7.25 mmol). After 30 min at 0° C., water followed by EA were added. The org. layer was extracted with EA (3×20 mL) and the combined org. layers were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. Purification of the residue by FC (1:1 hept-EA) gave the title compound as a yellow oil: TLC: rf (1:1 hept-EA)=0.33. LC-MS-conditions 07: tR=0.87 min, [M+H]+=260.06.

Workup

  1. stirringthe resulting mixture was stirred for 20 min at −70° C
  2. extractionlayer was extracted with EA (3×20 mL)
  3. dry with materiallayers were dried over MgSO4
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-596c1ad227dc4772825cd7c863544c75
Source dataset
uspto-grants-2014_09
Patent number
US08846733B2

Reaction notes

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