Imidazole → HCID 67981942, compound

HRID 595377Notes

Reaction equation

HRID 595377 reaction equation
[F:1][CH:2]([F:24])[C@H:3]1[O:11][C@H:10]2[C@H:6]([N:7]=[C:8]([N:12]([CH2:20][CH3:21])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[S:9]2)[C@@H:5]([OH:22])[C@@H:4]1[OH:23].N1C=CN=C1.[CH3:30][C:31]([Si:34](Cl)([CH3:36])[CH3:35])([CH3:33])[CH3:32]>CN(C=O)C>[Si:34]([O:22][C@@H:5]1[C@H:6]2[N:7]=[C:8]([N:12]([CH2:20][CH3:21])[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[S:9][C@H:10]2[O:11][C@H:3]([CH:2]([F:1])[F:24])[C@H:4]1[OH:23])([C:31]([CH3:33])([CH3:32])[CH3:30])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 123185579HCID 123185579, compound

Product 1

HCID 67981942HCID 67981942, compoundYield 66.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of tert-butyl (-(3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-6,7-dihydroxy-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl)(ethyl)carbamate (500 mg, 1.3 mmol) and imidazole (277 mg, 4 mmol) in DMF (20 mL) was treated with TBDMSCl (611 mg, 4 mmol) for 3 h at 40° C. The resulting solution was then cooled to room temperature, quenched by satd. aqueous NaHCO3 (50 mL) solution, extracted with DCM (3×20 mL), washed with brine (3×10 mL), dried over anhydrous MgSO4, and concentrated under vacuum to give a residue, which was purified by a silica gel column, eluted with 5%10% EtOAc in petroleum ether to afford tert-butyl(3 aR,5S,6R,7R,7aR)-7-(tert-butyldimethylsilyloxy)-5-(difluoromethyl)-6-hydroxy-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-yl(ethyl)carbamate as a light yellow syrup (420 mg, 64%). (ES, m/z): [M+1]+ 483.0; 1H NMR (300 MHz, CDCl3) δ 5.87 (d, J=5.4 Hz, 1H), 5.98 (td, J=55.2 Hz, 3.6 Hz, 1H), 4.10-3.91 (m, 5H), 3.77-3.70 (m, 1H), 1.56 (s, 9H), 1.21 (t, J=6.9 Hz, 3H), 0.94 (s, 9H), 0.19 (s, 3H), 0.15 (s, 3H).

Workup

  1. customquenched by satd
  2. extractionaqueous NaHCO3 (50 mL) solution, extracted with DCM (3×20 mL)
  3. washwashed with brine (3×10 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated under vacuum
  6. customto give a residue, which
  7. customwas purified by a silica gel column
  8. washeluted with 5%10% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-62c6372a606b46b6a992075e3fac15f0
Source dataset
uspto-grants-2016_01
Patent number
US09243020B2

Reaction notes

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