Imidazole → HCID 86596965, compound

HRID 2225287Notes

Reaction equation

HRID 2225287 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[OH:9][C@@H:10]1[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C@H:12]([CH2:27][OH:28])[CH2:11]1.N1C=CN=C1>CN(C=O)C>[Si:1]([O:28][CH2:27][C@@H:12]1[CH2:11][C@H:10]([OH:9])[CH2:15][CH2:14][C@@H:13]1[NH:16][C:17](=[O:26])[O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86596907HCID 86596907, compound

Product 1

HCID 86596965HCID 86596965, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

tert-Butyldimethylsilylchloride (2.78 g, 18.5 mmol) in DMF (30 mL) was added dropwise over 3 h to the alcohol from Step 1 (5.43 g) and imidazole (1.33 g) in DMF (50 mL) at 0° C. After the addition was complete the ice bath was removed and the reaction warmed to room temperature overnight. The DMF solution was diluted with ether (400 mL) then washed with water (2×75 mL), sat'd NaHCO3 (1×75 mL), and brine (1×075 mL). The organic layer was dried over MgSO4, filtered, and then evaporated to dryness. The product was purified by flash chromatography (silica gel, 20-40% ethyl acetate/hexanes) to provide benzyl (1S,2R,4R)-2-((tert-butyldimethylsilyloxy)methyl)-4-hydroxycyclohexylcarbamate (4.15 g) as a color less oil. MS found: (M+H)+=394.

Workup

  1. additionAfter the addition
  2. customwas removed
  3. additionThe DMF solution was diluted with ether (400 mL)
  4. washthen washed with water (2×75 mL), sat'd NaHCO3 (1×75 mL), and brine (1×075 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe product was purified by flash chromatography (silica gel, 20-40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4ae69351b5b64124bd08c020295023ef
Source dataset
uspto-grants-2008_05
Patent number
US07378409B2

Reaction notes

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