Imidazole → HCID 178455330, compound

HRID 2205642Notes

Reaction equation

HRID 2205642 reaction equation
[OH:1][C@@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[O:19])[CH2:13]3)[C:9]2=[O:28])[CH2:4][CH2:3]1.N1C=CN=C1.[Si:34](Cl)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].CCCCCCC>CN(C)C=O>[Si:34]([O:1][C@@H:2]1[CH2:3][CH2:4][C@H:5]([N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][CH2:21][C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)=[O:19])[CH2:13]3)[C:9]2=[O:28])[CH2:6][CH2:7]1)([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 8900HeptaneHCID 28928tert-Butyldimethylsilyl chlorideHCID 178525120HCID 178525120, compound

Product 1

HCID 178455330HCID 178455330, compoundYield 71.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of benzyl 2-(cis-4-hydroxycyclohexyl)-1-oxo-2,7-diazaspiro[4.5]decane-7-carboxylate (60.00 g, 155.2 mmol) in anhydrous N,N-dimethylformamide (160 mL) at r.t. was added 1H-imidazole (32.0 g, 466 mmol) and tert-butyldimethylsilyl chloride (36.2 g, 233 mmol). The reaction mixture was stirred at r.t. for 4 h, quenched with water (150 mL), and extracted with EtOAc (3×150 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product (84 g). The pure product (55.4 g) was obtained by re-crystallization of the crude product from heptane. The mother liquor was concentrated and subjected to purification by flash chromatography on a silical gel column eluting with AcOEt/Haxane to give additional 14.4 g of the product with a total 89.7% yield.

Workup

  1. customquenched with water (150 mL)
  2. extractionextracted with EtOAc (3×150 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford the crude product (84 g)

Sources & evidence

ORD record
ord-1d99f4ca1e22401c8fe8d7da002cc85b
Source dataset
uspto-grants-2016_06
Patent number
US09371323B2

Reaction notes

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