Methyl thiocyanate → HCID 42642984, compound

HRID 1888932Notes

Reaction equation

HRID 1888932 reaction equation
[SH:1][C@@:2]([CH3:9])([CH:6]([CH3:8])[CH3:7])[C:3](O)=[O:4].[CH3:10][S:11][C:12]#[N:13].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1>[CH:6]([C@:2]1([CH3:9])[S:1][C:12]([S:11][CH3:10])=[N:13][C:3]1=[O:4])([CH3:8])[CH3:7]

Participants

5

Reactant 3

HCID 11168Methyl thiocyanateHCID 516892Sodium BicarbonateHCID 42642983HCID 42642983, compound

Product 1

HCID 42642984HCID 42642984, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
23 °C

Procedure

(S)-2-Mercapto-2,3-dimethylbutanoic acid (1.5 g, 0.01 mol) was dissolved in toluene (15 mL) under an atmosphere of nitrogen. Activated 3A sieves (1.5 g) and MeSCN (1.1 mL, 0.015 mol) were added and the resultant mixture was warmed to 110° C. The mixture was stirred for 2 h and cooled to 23° C. The mixture was treated with saturated aqueous NaHCO3 (20 mL), the phases were separated and the aqueous phase was extracted with EtOAc (3×15 mL). The combined organic phases were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Chromatographic purification (10 g silica gel, 20-30% EtOAc/Hexanes) of the residual material yielded (S)-5-isopropyl-5-methyl-2-(methylthio)thiazol-4(5H)-one. This material was dissolved in MeOH (15 mL) and (S)-exo-aminonorbornane (1.35 g, 0.015 mol, 99.3% ee) was added under an atmosphere of nitrogen. The solution was stirred for 4 h and concentrated. Chromatographic purification (10 g silica gel, 10-40% EtOAc/Hexanes) of the residual material yielded 1.73 g (64%) of the title compound. 1H NMR (400 MHz, CDCl3, 90.15/9.85 mixture of diastereomers, signals for the major diastereomer) δ 3.33-3.40 (m, 1H), 2.36-2.45 (m, 2H), 2.21 (septaplet, 1H, J=8 Hz), 1.84-1.91 (m, 1H), 1.60-1.83 (m, 1H), 1.42-1.68 (m, 3H), 1.62 (s, 3H), 1.13-1.30 (m, 4H), 1.05 (d, 3H, J=8 Hz), 0.90 (d, 3H, J=8 Hz); 13C NMR (100 MHz, CDCl3, 90.15/9.85 mixture of diastereomers, signals for the major diastereomer) δ 191.1, 180.9, 70.9, 59.5, 43.0, 38.5, 35.9, 35.7, 35.6, 28.2, 26.6, 25.6, 19.0, 18.4; IR (neat): 3168, 2959, 2869, 1696, 1585, 1440, 1327, 1256, 1090, 1017, 829 cm−1; Exact Mass (C14H22N2OS+H): calculated=267.1526, measured=267.1525. Chiral LC: 90.15/9.85 dr.

Workup

  1. customthe phases were separated
  2. extractionthe aqueous phase was extracted with EtOAc (3×15 mL)
  3. washThe combined organic phases were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customChromatographic purification (10 g silica gel, 20-30% EtOAc/Hexanes) of the residual material

Sources & evidence

ORD record
ord-5a1ebc8869764507a532c4d3f663bba4
Source dataset
uspto-grants-2013_08
Patent number
US08501954B2

Reaction notes

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