Methyl iodide → (SR)-2-((RS)-2,2-dimethyl-1,3-dioxolan-4-yl)-N-methyl-3-(methylthio)propan-1-amine

HRID 390092Notes

Reaction equation

HRID 390092 reaction equation
[CH3:1][C:2]1([CH3:23])[O:6][CH:5]([CH:7]([CH2:20][S:21][CH3:22])[CH2:8][NH:9][C:10](=O)OCC2C=CC=CC=2)[CH2:4][O:3]1.[H-].[Na+].CI.[OH-].[K+]>C1COCC1.C(O)(C)C.C(Cl)Cl.O.C(Cl)(Cl)Cl>[NH3:9].[CH3:2][OH:3].[CH3:1][C:2]1([CH3:23])[O:6][CH:5]([CH:7]([CH2:20][S:21][CH3:22])[CH2:8][NH:9][CH3:10])[CH2:4][O:3]1

Participants

11

Reactant 4

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 86651336HCID 86651336, compound

Product 2

HCID 21705897Ammonia methanolYield 7%HCID 66953538(SR)-2-((RS)-2,2-dimethyl-1,3-dioxolan-4-yl)-N-methyl-3-(methylthio)propan-1-amineYield 154.8%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of benzyl (SR)-2-((RS)-2,2-dimethyl-1,3-dioxolan-4-yl)-3-(methylthio)propylcarbamate (210 mg, 619 μmol) in dry THF (5 mL) was added sodium hydride 60% (34.6 mg, 866 μmol) and then methyl iodide (77 μl, 1237 μmol) and the mixture was stirred RT under argon for 30 mins. Chloroform was added followed by water. Normal processing afforded a syrup. Potassium hydroxide (1.0 g, 1.78E+04 μmol) was added to this material in isopropanol (8 mL) and the resulting solution was heated under reflux for 5 h. Silica gel was added, the mixture was concentrated to dryness and applied to a silica column. Elution with 5% MeOH/CH2Cl2 and then 7% 7N NH3/MeOH in CH2Cl2 gave (SR)-2-((RS)-2,2-dimethyl-1,3-dioxolan-4-yl)-N-methyl-3-(methylthio)propan-1-amine (105 mg, 479 μmol, 77% yield) as a syrup. 1H NMR δ 4.19 (1H, dd, J=6.7, 13.4 Hz); 4.06 (1H, dd, J=6.3, 8.1 Hz); 3.70 (1H, dd, J=7.3, 8.0 Hz); 2.76 (1H, dd, J=4.4, 13.1 Hz); 2.70-2.56 (3H, m); 2.42 (3H, s); 2.12 (3H, s); 1.97-1.87 (1H, m); 1.40 (3H, s); 1.34 (3H, s). 13C NMR (CDCl3) δ 109.0, 77.1, 68.0, 52.6, 42.2, 37.2, 34.5, 27.0, 25.7, 16.8.

Workup

  1. customNormal processing afforded a syrup
  2. temperaturethe resulting solution was heated
  3. temperatureunder reflux for 5 h
  4. additionSilica gel was added
  5. concentrationthe mixture was concentrated to dryness
  6. washElution with 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-9aaa17a08773451b8ce195d6eb3814f0
Source dataset
uspto-grants-2013_02
Patent number
US08383636B2

Reaction notes

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