Ethyl Acetate → HCID 86719969, compound

HRID 1617329Notes

Reaction equation

HRID 1617329 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[CH:11]=[CH:10][CH:9]=[N:8]1.C([Li])(C)(C)C.[C:17]([C:20]1[CH:32]=[CH:31][C:23]2[N:24]([CH2:28][O:29][CH3:30])[C:25](=[O:27])[S:26][C:22]=2[CH:21]=1)(=[O:19])[CH3:18].CCOC(C)=O>C1COCC1>[OH:19][C:17]([C:20]1[CH:32]=[CH:31][C:23]2[N:24]([CH2:28][O:29][CH3:30])[C:25](=[O:27])[S:26][C:22]=2[CH:21]=1)([C:11]1[N:7]([CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][O:1]2)[N:8]=[CH:9][CH:10]=1)[CH3:18]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 218663101-(2-Tetrahydropyranyl)-1H-pyrazoleHCID 86719968HCID 86719968, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 86719969HCID 86719969, compoundYield 84.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Add 1-tetrahydropyran-2-yl-pyrazole (1.5 Eq, 202 mmoles, 30.8 g)(Aldrich) and THF (900 mL) to a flame dried 2 L 3 neck round bottom flask and cool to −78° C. (dry ice/acetone bath). Add t-butyl lithium (2.5 M in THF)(1.5 Eq, 202 mmoles; 81.0 mL) dropwise, maintaining at least −68° C., and stir for 60 min at −78° C. Add a solution of 6-acetyl-3-(methoxymethyl)-3H-1,3-benzothiazol-2-one (32.0 g, 134 mmoles) in THF (450 mL) dropwise over 45 min, and stir at −78 for 30 min. Remove the dry ice bath and allow to warm to −50° C. and stir for 1 hr. (do not let temp. rise above −45° C.). Quench the reaction with MeOH (80 mL). Transfer to a separatory funnel, add EtOAc (2000 mL), and wash with water (500 mL) and then brine (500 mL). The organic layer is dried over Na2SO4, filter and concentrate to give a crude yellow oil. Purify the material by HPLC, eluting with hexanes/EtOAc (6:4) to yield 6-[1-hydroxy-1-(1-tetrahydropyran-2-yl-1H-pyrazol-5-yl)ethyl]-3-(methoxymethyl)-3H-1,3-benzothiazol-2-one as a white foam (44 g, 113 mmoles, 84% yield) (Racemic mixture of diasteromers). LCMS (Low) rt=1.76 min., M+1=288, and rt=1.86 min., M+1=288

Workup

  1. dry with materialdried 2 L 3 neck round bottom flask
  2. stirringstir at −78 for 30 min
  3. customRemove the dry ice bath
  4. temperatureto warm to −50° C.
  5. stirringstir for 1 hr
  6. customrise above −45° C.
  7. customQuench
  8. customthe reaction with MeOH (80 mL)
  9. washwash with water (500 mL)
  10. dry with materialThe organic layer is dried over Na2SO4
  11. filtrationfilter
  12. concentrationconcentrate
  13. customto give a crude yellow oil
  14. customPurify the material by HPLC
  15. washeluting with hexanes/EtOAc (6:4)
  16. customto yield

Sources & evidence

ORD record
ord-b706508f677b4afbbd7397567fa28b3b
Source dataset
uspto-grants-2014_07
Patent number
US08765960B2

Reaction notes

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