Methyl Acetate → HCID 86705559, compound

HRID 2279573Notes

Reaction equation

HRID 2279573 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH3:17])(=[O:15])[CH3:14].[F:18][CH:19]([F:35])[O:20][C:21]1[CH:34]=[CH:33][C:24](/[CH:25]=[N:26]/[S@:27]([C:29]([CH3:32])([CH3:31])[CH3:30])=[O:28])=[CH:23][CH:22]=1>C1COCC1>[F:35][CH:19]([F:18])[O:20][C:21]1[CH:22]=[CH:23][C:24]([C@H:25]([NH:26][S@:27]([C:29]([CH3:31])([CH3:30])[CH3:32])=[O:28])[CH2:14][C:13]([O:16][CH3:17])=[O:15])=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 6584Methyl AcetateHCID 7912DiisopropylamineHCID 88924999HCID 88924999, compoundHCID 178418339Butyllithium

Product 1

HCID 86705559HCID 86705559, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of diisopropylamine (16.70 mL, 119.1 mmol) in THF (80 mL) at 0° C. was added dropwise 2.5M n-butyllithium (48.82 mL, 122.0 mmol) and stirring was continued for 15 min. The solution was cooled to −78° C. and methyl acetate (9.219 mL, 116.2 mmol) was added dropwise and stirring continued for 30 min. A solution of Ti(O-iPr)3Cl (58.30 mL, 244.1 mmol) in THF (20 mL) was introduced dropwise at −78° C. and stirring was continued for 45 min. A solution of 378 (16 g, 58.12 mmol) in THF (20 mL) was then added dropwise and stirring was continued for 3 h. The reaction was quenched at −78° C. by dropwise addition of satd. aq. NH4Cl and warmed to RT. The mixture was thrice extracted with EtOAc, washed with brine, dried (MgSO4), and concentrated. The crude product was purified by SiO2 chromatography eluting with an EtOAc/hexane gradient (20 to 60% EtOAc) to afford 8.67 g (43%) of (R)-methyl 3-(4-(difluoromethoxy)phenyl)-3-((S)-1,1-dimethylethylsulfinamido)propanoate (380) as a low melting white solid along with 9.67 g impure material.

Workup

  1. stirringstirring
  2. waitcontinued for 30 min
  3. stirringstirring
  4. waitwas continued for 45 min
  5. stirringstirring
  6. waitwas continued for 3 h
  7. customThe reaction was quenched at −78° C. by dropwise addition of satd
  8. temperatureaq. NH4Cl and warmed to RT
  9. extractionextracted with EtOAc
  10. washwashed with brine
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated
  13. customThe crude product was purified by SiO2 chromatography
  14. washeluting with an EtOAc/hexane gradient (20 to 60% EtOAc)

Sources & evidence

ORD record
ord-99cf1f1118604c56b30520fddbd423d5
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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