Sodium hydride → HCID 58993646, compound

HRID 391436Notes

Reaction equation

HRID 391436 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12]Br)[CH:11]=1)[C:5]([O:7]C)=[O:6].[OH:14][CH2:15][C:16]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1.[H-].[Na+].O.[OH-].[Li+]>CN(C)C=O.CO>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([CH2:12][O:14][CH2:15][C:16]2([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:27])([CH3:28])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH:11]=1)[C:5]([OH:7])=[O:6]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 168937Lithium hydroxide, monohydrateHCID 9994433Tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylateHCID 58993494Methyl 3-bromo-5-(bromomethyl)benzoate

Product 1

HCID 58993646HCID 58993646, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 3-bromo-5-(bromomethyl)benzoate (2.1 g, 6.81 mmol) and tert-butyl 4-(hydroxymethyl)-4-phenylpiperidine-1-carboxylate (1.8 g, 6.2 mmol) were combined in dimethylformamide (21 mL) and cooled to 0° C. The reaction was treated with sodium hydride (298 mg, 12.4 mmol), stirred at 0° C. for 1 h, and at room temperature for 30 min. The reaction was cooled to 0° C. and treated lithium hydroxide monohydrate (0.54 g, 13.6 mmol). The solution was stirred at room temperature for 16 h and the solvents evaporated. The resultant residue was diluted with water (10 mL) and the pH adjusted to ca. 1 with 1 N hydrochloric acid. The resultant white suspension was stored at 4° C. overnight and the product was collected by filtration, washed with a small amount of water, and dried in vacuo for several hours to afford 2.4 g (70%) as a white powder. LC/MS: tR=3.33 min, 506.20 (MH)+. (Phenomenex C18 4.6×50 mm, 10% MeOH/90% H2O/0.1% TFA→90% MeOH/10% H2O/0.1% TFA, Gradient time=4 min., Flow rate=4 mL/min.).

Workup

  1. waitat room temperature for 30 min
  2. temperatureThe reaction was cooled to 0° C.
  3. stirringThe solution was stirred at room temperature for 16 h
  4. customthe solvents evaporated
  5. additionThe resultant residue was diluted with water (10 mL)
  6. waitThe resultant white suspension was stored at 4° C. overnight
  7. filtrationthe product was collected by filtration
  8. washwashed with a small amount of water
  9. customdried in vacuo for several hours
  10. customto afford 2.4 g (70%) as a white powder

Sources & evidence

ORD record
ord-177751f7f77a4656aef6837f1dc8a9fd
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

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