Sodium hydride → HCID 44477166, compound

HRID 2361663Notes

Reaction equation

HRID 2361663 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][CH2:9][N:8]([C:12]([N:14]3[CH2:17][CH:16]([OH:18])[CH2:15]3)=[O:13])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1>C1COCC1>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][O:18][CH:16]2[CH2:15][N:14]([C:12]([N:8]3[CH2:9][CH2:10][CH2:11][N:5]([CH:1]4[CH2:4][CH2:3][CH2:2]4)[CH2:6][CH2:7]3)=[O:13])[CH2:17]2)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 693291-(Bromomethyl)-4-chlorobenzeneHCID 44462713HCID 44462713, compound

Product 1

HCID 44477166HCID 44477166, compoundYield 51.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 1-[(4-cyclobutyl-1,4-diazepan-1-yl)carbonyl]azetidin-3-ol (40 mg, 0.158 mmol) in THF (3 mL) was added NaH (13 mg, 0.316 mmol, 60% in mineral oil). The suspension was stirred at RT for 1 h before 1-(bromomethyl)-4-chlorobenzene (65 mg, 0.316 mmol) was added in one portion. The resulting mixture was heated at 80° C. for 1 H, cooled to RT and concentrated at reduced pressure. The crude residue was dissolved in MeOH and filtered through a short pad of silica before purification by preparative HPLC to provide the title compound (31 mg, 40%) as colourless oil.

Workup

  1. additionwas added in one portion
  2. temperaturecooled to RT
  3. concentrationconcentrated at reduced pressure
  4. dissolutionThe crude residue was dissolved in MeOH
  5. filtrationfiltered through a short pad of silica before purification by preparative HPLC

Sources & evidence

ORD record
ord-9ec31907388a49799055cce12e126cd9
Source dataset
uspto-grants-2014_04
Patent number
US08691804B2

Reaction notes

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