Methyl Acetate → Methyl 3-(4-butoxyphenyl)-3-((tert-butylsulfinyl)amino)butanoate

HRID 1629798Notes

Reaction equation

HRID 1629798 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH3:17])(=[O:15])[CH3:14].[CH2:18]([O:22][C:23]1[CH:28]=[CH:27][C:26](/[C:29](=[N:31]\[S:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])/[CH3:30])=[CH:25][CH:24]=1)[CH2:19][CH2:20][CH3:21]>C1COCC1.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[CH2:18]([O:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([NH:31][S:32]([C:34]([CH3:36])([CH3:35])[CH3:37])=[O:33])([CH3:30])[CH2:14][C:13]([O:16][CH3:17])=[O:15])=[CH:25][CH:24]=1)[CH2:19][CH2:20][CH3:21]

Participants

7

Reactant 4

HCID 6584Methyl AcetateHCID 7912DiisopropylamineHCID 89599479(NZ)-N-[1-(4-butoxyphenyl)ethylidene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 86685892Methyl 3-(4-butoxyphenyl)-3-((tert-butylsulfinyl)amino)butanoateYield 87%

Reagents, catalysts & solvents 2

HCID 11673339ChlorotitaniumtriisopropoxideCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

To a stirred solution of diisopropylamine (3.86 mL, 27.1 mmol) in THF (40 mL) at −78° C. was added n-butyllithium (22.57 mL, 27.1 mmol) dropwise. The reaction was slowly warmed up to −20° C. and stirred for 45 min. The reaction was cooled to −78° C. and methyl acetate (2.006 g, 27.1 mmol) was added dropwise. After 30 min, chlorotitanium triisopropoxide (8.09 mL, 33.8 mmol) in THF (40 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h. Intermediate 107A (4 g, 13.54 mmol) in THF (15 mL) was added dropwise and the reaction was stirred at −78° C. for 2 h. The reaction was quenched by addition of sat'd NH4Cl solution and stirred vigorously while warmed to rt. The mixture was filtered through Celite® and washed with EtOAc. The filtrate was washed with H2O, brine, dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography (220 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (4.33 g, 87%) as a light yellow oil. LCMS Anal. Calc'd for C19H31NO4S 369.20, found [M+H] 370.2. 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J=8.80 Hz, 2H), 6.85 (d, J=8.80 Hz, 2H), 3.95 (t, J=6.46 Hz, 2H), 3.62 (s, 3H), 2.05 (s, 2H), 1.74-1.80 (m, 2H), 1.74 (s, 3H), 1.44-1.54 (m, 2H), 1.29 (s, 9H), 0.98 (t, J=7.43 Hz, 3H).

Workup

  1. temperatureThe reaction was cooled to −78° C.
  2. waitAfter 30 min
  3. stirringThe reaction was stirred at −78° C. for 1 h
  4. stirringthe reaction was stirred at −78° C. for 2 h
  5. customThe reaction was quenched by addition of sat'd NH4Cl solution
  6. stirringstirred vigorously
  7. temperaturewhile warmed to rt
  8. filtrationThe mixture was filtered through Celite®
  9. washwashed with EtOAc
  10. washThe filtrate was washed with H2O, brine
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by silica gel chromatography (220 g silica gel, eluted with EtOAc in hexanes)

Sources & evidence

ORD record
ord-eb3408075617490485f3b32edf1b2793
Source dataset
uspto-grants-2014_07
Patent number
US08791091B2

Reaction notes

Loading…