Methyl Acetate → 3-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester

HRID 1971319Notes

Reaction equation

HRID 1971319 reaction equation
N(C(C)C)C(C)C.[Li]CCCC.[CH3:13][O:14][C:15](=[O:17])[CH3:16].[C:18]1([CH:24]=[N:25][S:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH4+].[Cl-]>C1COCC1.O>[CH3:13][O:14][C:15](=[O:17])[CH2:16][CH:24]([NH:25][S:26]([C:28]([CH3:31])([CH3:30])[CH3:29])=[O:27])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 5

HCID 6584Methyl AcetateHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 673910032-methyl-N-benzylidene-propane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 684444833-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×

Conditions

Temperature
-78 °C

Procedure

Under anhydrous conditions a solution of i-Pr2NH (2.2 eq) in 60 mL THF is cooled to 0° C. (J. Org. Chem. 2003, 68, 9948-9957). n-BuLi (2.1 eq, 1.6 M solution in hexane) is added via syringe and the solution is stirred for 30 min. The solution is then cooled to −78° C. A solution of acetic acid methyl ester (2 eq) in 1 mL of THF is added via syringe and the reaction solution is stirred for 30 min. To this solution is added ClTi(Oi-Pr)3 (4.2 eq) in 20 mL THF and the solution is stirred for 30 min. A solution of the tert.-butane-sulfinic acid 1-phenyl-methylidene amide (5.4 mmol, 1 eq) in 5 mL THF is slowly added via syringe and the solution is stirred for 3 h at −78° C. Upon reaction completion as determined by TLC, a saturated aqueous solution of NH4Cl (5 mL) is added and the suspension is warmed to room temperature. The mixture is diluted with H2O and vigorously stirred to dissolve the precipitate. The mixture is then decanted into a separatory funnel, and the remaining solid is diluted with equal parts of H2O and ethyl acetate and vigorously stirred for 15 min. The mixture is then added to the separatory funnel and the organic layer is collected. The aqueous layer is then extracted 3× with ethyl acetate. The combined organic layers are washed with brine, dried with Na2SO4, and concentrated in vacuo. 3-(2-Methyl-propane-2-sulfinylamino)-3-phenyl-propionic acid methyl ester is obtained as a clear colourless solid (102% yield); ES-MS (MH+)=284.1; 1H-NMR (DMSO-d6, 400 MHz): δ [ppm] 7.35-7.23 (m, 5H), 5.59 (d, 1H, 6.1 Hz), 4.63 (m, 1H), 3.54 (s, 3H), 3.04-2.99 (m, 1H), 2.80-2.74 (m, 1H), 1.06 (s, 9H).

Workup

  1. stirringthe reaction solution is stirred for 30 min
  2. stirringthe solution is stirred for 30 min
  3. stirringthe solution is stirred for 3 h at −78° C
  4. customUpon reaction completion
  5. temperaturethe suspension is warmed to room temperature
  6. stirringvigorously stirred
  7. dissolutionto dissolve the precipitate
  8. customThe mixture is then decanted into a separatory funnel
  9. additionthe remaining solid is diluted with equal parts of H2O and ethyl acetate
  10. stirringvigorously stirred for 15 min
  11. additionThe mixture is then added to the separatory funnel
  12. customthe organic layer is collected
  13. extractionThe aqueous layer is then extracted 3× with ethyl acetate
  14. washThe combined organic layers are washed with brine
  15. dry with materialdried with Na2SO4
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-91346bfe493744e58428841f9160a670
Source dataset
uspto-grants-2013_04
Patent number
US08431602B2

Reaction notes

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