Thiazole → 1-(1,3-Thiazol-2-yl)cyclobutan-1-ol

HRID 1760262Notes

Reaction equation

HRID 1760262 reaction equation
[Li]CCCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[C:11]1(=[O:15])[CH2:14][CH2:13][CH2:12]1.[NH4+].[Cl-]>CCCCCC.CCOCC>[OH:15][C:11]1([C:7]2[S:6][CH:10]=[CH:9][N:8]=2)[CH2:14][CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 9256ThiazoleHCID 14496CyclobutanoneHCID 25517Ammonium ChlorideHCID 178418339Butyllithium

Product 1

HCID 129928101-(1,3-Thiazol-2-yl)cyclobutan-1-olYield 43.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8058HexaneSolvent

Procedure

To a solution of n-BuLi (36 mL of a 2.5M solution in hexane, 90 mmol) in anhydrous ether (100 mL) at −78° C. was slowly added a solution of thiazole (6.35 g, 74.6 mmol) in anhydrous ether (60 mL). The resulting mixture was stirred for 1 h and then cyclobutanone (10.4 g, 148 mmol) in ether (20 mL) was added over 5 min. The mixture was stirred for 2 h at −78° C. and then sat. aq. NH4Cl was added and the phases were separated. The aqueous phase was extracted with ethyl acetate (3×) and the combined organics were washed with water, brine, dried (MgSO4) and concentrated. Flash chromatography of the residue (silica gel; hexane/ethyl acetate 4:1 to 7:3) provided 2-[(1-Hydroxy)cyclobutyl]thiazole (5 g).

Workup

  1. stirringThe mixture was stirred for 2 h at −78° C.
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  4. washthe combined organics were washed with water, brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-be89cb4efda04cbfa28f64490f51b01a
Source dataset
uspto-grants-2005_01
Patent number
US06841564B2

Reaction notes

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