Water → Aprikalim

HRID 1956782Notes

Reaction equation

HRID 1956782 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@H:7]2[CH2:12][CH2:11][CH2:10][CH2:9][S@:8]2=[O:13])[CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:24][N:25]=[C:26]=[S:27].O>O1CCCC1>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@:7]2([C:26](=[S:27])[NH:25][CH3:24])[CH2:12][CH2:11][CH2:10][CH2:9][S@:8]2=[O:13])[CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 11167Methyl isothiocyanateHCID 2733832Lithium HexamethyldisilazideHCID 15147289(1R,2R)-2-(3-pyridyl)tetrahydro-2H-thiopyran 1-oxide

Product 1

HCID 9571083AprikalimYield 73.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A stirred suspension of (1R,2R)-2-(3-pyridyl)tetrahydro-2H-thiopyran 1-oxide (50.0 g) in dry tetrahydrofuran (500 ml) is treated with a solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (281 ml;1M) at between -5° C. and +5° C. The resulting suspension is stirred for 15 minutes at between -5° C. and +50C. and then it is treated with a solution of methyl isothiocyanate (20.26 g) in dry tetrahydrofuran (63 ml) at between -5° C. and +50C. The mixture is stirred at between -5° C. and +5° C. for 30 minutes and then it is treated with water (500 ml). The aqueous phase is then washed with dichloromethane (2×150 ml), The aqueous solution is then treated with charcoal, filtered, neutralised by treatment with dilute hydrochloric acid (2N) and filtered, to give (1R,2R)-2-(3-pyridyl)-N-methyltetrahydro-2H-thiopyran-2-carbothioamide 1-oxide (50.64 g), in the form of a white powder, m.p. 215°-216° C., enantiomeric excess greater than 99.6%. [NMR (CDCl3):- 1.6(m,1H), 1.7(m,2H),2.2(m, 1H),2.3(m, 1H),2.9(m,1H), 3.0(m,1H),3.1 (d,3H),3.7(m,1H),7.3(m,1H), 8.1 (m,1H),8.3(m,1H),8.5(m,1H),8.7(m,1H)]; specific rotations (sodium D line) -205° (c=1, 28° C., CHCl3); -281° (c=1, 31° C., EtOH).

Workup

  1. washThe aqueous phase is then washed with dichloromethane (2×150 ml)
  2. additionThe aqueous solution is then treated with charcoal
  3. filtrationfiltered
  4. filtrationfiltered

Sources & evidence

ORD record
ord-a53da0798e9e4ac7bb8997444ca2ee79
Source dataset
uspto-grants-1998_07
Patent number
US05780636

Reaction notes

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