Acetone → Tert-butyl 5-(2-hydroxypropan-2-yl)-4-(2-(tetrahydro-2h-pyran-2-yloxy)ethyl)thiazol-2-ylcarbamate

HRID 254669Notes

Reaction equation

HRID 254669 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[O:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH:22]1[O:27][CH2:28][CH2:29][C:30]1[N:31]=[C:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[S:33][CH:34]=1.[CH3:43][C:44]([CH3:46])=[O:45]>C1COCC1>[OH:45][C:44]([C:34]1[S:33][C:32]([NH:35][C:36](=[O:42])[O:37][C:38]([CH3:39])([CH3:41])[CH3:40])=[N:31][C:30]=1[CH2:29][CH2:28][O:27][CH:22]1[CH2:23][CH2:24][CH2:25][CH2:26][O:21]1)([CH3:46])[CH3:43]

Participants

7

Reactant 5

HCID 180AcetoneHCID 7912DiisopropylamineHCID 2724682Lithium diisopropylamideHCID 87179369Tert-butyl 4-(2-(tetrahydro-2h-pyran-2-yloxy)ethyl)thiazol-2-ylcarbamateHCID 178418339Butyllithium

Product 1

HCID 87179654Tert-butyl 5-(2-hydroxypropan-2-yl)-4-(2-(tetrahydro-2h-pyran-2-yloxy)ethyl)thiazol-2-ylcarbamateYield 53.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of diisopropylamine (9.5 mL, 67.2 mmol) in THF (100 ml) was added butyllithium (42 mL, 1.6M in hexanes, 67.2 mmol) drop wise at −78° C. and stirred for 30 min. Thus obtained LDA solution was immediately added by cannulation to a solution of Example 89C (7.36 g, 22.4 mmol) in THF (100 ml) at −78° C. and stirred for 30 min at the same temperature. Then, dry acetone (8.2 ml, 112 mmol, Acros) was added slowly and the reaction mixture was removed from cold bath and allowed to reach room temperature for overnight while stirring. The reaction mixture was quenched with saturated aqueous NH4Cl solution (100 mL) and the aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by column chromatography (SiO2, 0-100% ethyl acetate in hexanes) to afford 4.6 g (53%) of the title compound. MS (ESI+) m/z 387 (M+H)+

Workup

  1. stirringstirred for 30 min at the same temperature
  2. customthe reaction mixture was removed from cold bath
  3. waitto reach room temperature for overnight
  4. stirringwhile stirring
  5. customThe reaction mixture was quenched with saturated aqueous NH4Cl solution (100 mL)
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×100 mL)
  7. dry with materialThe combined organic extracts were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by column chromatography (SiO2, 0-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9f29881a9a194d27aa710c84dc155b63
Source dataset
uspto-grants-2011_01
Patent number
US07875640B2

Reaction notes

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