Sodium hydride → HCID 66974099, compound

HRID 1396025Notes

Reaction equation

HRID 1396025 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][CH2:13][OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Cl:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([CH2:12][CH2:13][O:14][CH2:22][C:21]2[CH:24]=[CH:25][C:18]([Cl:17])=[CH:19][CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 22594530tert-Butyl 3-(2-hydroxyethyl)azetidine-1-carboxylate

Product 1

HCID 66974099HCID 66974099, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution consisting of 3-(2-hydroxy-ethyl)-azetidine-1-carboxylic acid tert-butyl ester (0.250 g, 1.24 mmol) and THF (2 mL) at 0° C. was added sodium hydride (0.0459 g, 0.124 mmol). The reaction was stirred at 0° C. for 0.5 h, then treated with tetrabutylammonium iodide (0.0459 g, 0.124 mmol) and 4-chlorobenzyl bromide (0.383 g, 1.86 mmol), warmed to rt and stirred for 16 h. The reaction was quenched with saturated aqueous NH4Cl (1.0 mL), diluted with ethyl acetate (40 mL) and extracted with 1 N NaOH (40 mL). The organic layer was dried (MgSO4) and concentrated. The residue was purified (FCC) to give the title compound as a yellow oil (0.302 g, 74%). 1H NMR (d6-DMSO): 7.40 (d, J=8.4 Hz, 2H), 7.32 (d, J=8.4 Hz, 2H), 4.42 (s, 2H), 3.88 (t, J=8.0 Hz, 2H), 3.53-3.44 (m, 2H), 3.40 (t, J=6.2 Hz, 2H), 2.62-2.53 (m, 1H), 1.84-1.74 (m, 2H), 1.36 (s, 9H).

Workup

  1. temperaturewarmed to rt
  2. stirringstirred for 16 h
  3. customThe reaction was quenched with saturated aqueous NH4Cl (1.0 mL)
  4. additiondiluted with ethyl acetate (40 mL)
  5. extractionextracted with 1 N NaOH (40 mL)
  6. dry with materialThe organic layer was dried (MgSO4)
  7. concentrationconcentrated
  8. customThe residue was purified (FCC)

Sources & evidence

ORD record
ord-451573c60da040f1ab9542873d25c899
Source dataset
uspto-grants-2014_12
Patent number
US08901111B2

Reaction notes

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