Methylamine hydrochloride → (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate

HRID 1854239Notes

Reaction equation

HRID 1854239 reaction equation
[C:1]([O:4][C@H:5]1[C@H:10]([N:11]=[C:12]=[S:13])[C@@H:9]([O:14][C:15](=[O:17])[CH3:16])[C@H:8]([O:18][C:19](=[O:21])[CH3:20])[C@@H:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[O:6]1)(=[O:3])[CH3:2].Cl.[CH3:28][NH2:29]>CC#N>[C:1]([O:4][C@H:5]1[C@H:10]([NH:11][C:12]([NH:29][CH3:28])=[S:13])[C@@H:9]([O:14][C:15](=[O:17])[CH3:16])[C@H:8]([O:18][C:19](=[O:21])[CH3:20])[C@@H:7]([CH2:22][O:23][C:24](=[O:26])[CH3:25])[O:6]1)(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 6364545Methylamine hydrochlorideHCID 14130735(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanatotetrahydro-2H-pyran-2,4,5-triyl triacetate

Product 1

HCID 86638171(2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetateYield 63.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate (0.51 g, 1.32 mmol) (Jochims, J. C. et al, Tetrahedron, 1965, 21(9), 2611-16) in CH3CN, was added neat methylamine hydrochloride (0.18 g, 2.64 mmol). The reaction was stirred at room temperature until complete by TLC (1.5 h). The reaction was washed with a minimal amount of saturated aqueous NaHCO3 (15 mL). The aqueous layer was then extracted three times with DCM, and the organic layers were combined, dried with MgSO4, filtered and concentrated. The concentrated mixture was purified via flash column chromatography on silica gel (EtOAc:hexanes, 1:1), providing (2S,3R,4R,5S,6R)-6-(acetoxymethyl)-3-(3-methylthioureido)-tetrahydro-2H-pyran-2,4,5-triyl triacetate (0.35 g, 62% yield).1H NMR (500 MHz, CDCl3) δ 2.06 (s, 3H), 2.08 (s, 3H), 2.11 (s, 3H), 2.15 (s, 3H), 2.98 (s, 3H), 3.82-3.88 (m, 1H), 4.10-4.16 (m, 2H), 4.28 (dd, 1H, J=4.6, 12.5 Hz), 5.17-5.22 (m, 2H), 5.74 (d, 1H, J=8.1 Hz), 5.92 (s, 1H), 6.21 (s, 1H).

Workup

  1. washThe reaction was washed with a minimal amount of saturated aqueous NaHCO3 (15 mL)
  2. extractionThe aqueous layer was then extracted three times with DCM
  3. dry with materialdried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrated mixture was purified via flash column chromatography on silica gel (EtOAc:hexanes, 1:1)

Sources & evidence

ORD record
ord-6b32578cefc843968567da9c7601a4e7
Source dataset
uspto-grants-2015_02
Patent number
US08962664B2

Reaction notes

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