Bis(2-bromoethyl) ether → 4-[N-(diphenylmethylene)amino]tetrahydropyran-4-carboxylic acid benzyl ester

HRID 1976909Notes

Reaction equation

HRID 1976909 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11](=[O:27])[CH2:12][N:13]=[C:14]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Br[CH2:29][CH2:30][O:31][CH2:32][CH2:33]Br.C(OCC)(=O)C.CCCCCC>COCCOC>[CH2:3]([O:10][C:11]([C:12]1([N:13]=[C:14]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)=[O:27])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 4

HCID 21521Bis(2-bromoethyl) etherHCID 24758Sodium hydrideHCID 11782449Diphenylmethylene-Glycine benzyl esterHCID 21226206Ethyl acetate hexane2×

Product 1

HCID 537582684-[N-(diphenylmethylene)amino]tetrahydropyran-4-carboxylic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent4×

Procedure

To a suspension of sodium hydride (6.56 grams. 0.164 mole) in ethylene glycol dimethyl ether (150 mL) at 0° C. is added a solution of the N-(diphenylmethylene)glycine benzyl ester (0.07398 mole) in ethylene glycol dimethyl ether (50 mL) dropwise via addition funnel. A solution of 2-bromoethyl ether (23.21 grams, 0.090 mole) in ethylene glycol dimethyl ether (50 mL) is then added, in 10 mL portions over approximately 5 minutes, to the ethylene glycol dimethyl ether solution. The ice bath is removed and the reaction is stirred at room temperature for 16 hours. The mixture is diluted with diethyl ether and washed with water. The aqueous layer is extracted with diethyl ether. The combined organic extracts are washed with brine, dried over magnesium sulfate, and concentrated to afford crude product. Chromatography on silica gel eluting first with 4 L of 5% ethyl acetate/hexane followed by 4 liters of 10% ethyl acetate/hexane provides 4-[N-(diphenylmethylene)amino]tetrahydropyran-4-carboxylic acid benzyl ester as a clear yellow oil.

Workup

  1. additiondropwise via addition funnel
  2. customThe ice bath is removed
  3. additionThe mixture is diluted with diethyl ether
  4. washwashed with water
  5. extractionThe aqueous layer is extracted with diethyl ether
  6. washThe combined organic extracts are washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customto afford crude product

Sources & evidence

ORD record
ord-997b682f0e134b9795869f3e20107c47
Source dataset
uspto-grants-2001_05
Patent number
US06229025B1

Reaction notes

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