Sulfuric acid magnesium salt (1:1) → (2-Chloro-4-(tetrahydro-pyran-2-yloxy)-benzyl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amine

HRID 1827515Notes

Reaction equation

HRID 1827515 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.[N:17]1([CH2:22][CH2:23][O:24][C:25]2[CH:30]=[CH:29][C:28]([NH2:31])=[CH:27][CH:26]=2)[CH2:21][CH2:20][CH2:19][CH2:18]1.S([O-])([O-])(=O)=O.[Mg+2].[BH4-].[Na+]>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[CH:6][C:3]=1[CH2:4][NH:31][C:28]1[CH:29]=[CH:30][C:25]([O:24][CH2:23][CH2:22][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:26][CH:27]=1

Participants

7

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 64937494-(2-(Pyrrolidin-1-yl)ethoxy)anilineHCID 221373212-Chloro-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde

Product 1

HCID 22137435(2-Chloro-4-(tetrahydro-pyran-2-yloxy)-benzyl]-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-amineYield 71.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-chloro-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (1.68 g, 6.97 mmol) and 4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (1.37 g, 6.64 mmol) in 25 mL methylene chloride was added magnesium sulfate (2.81 g, 23.3 mmol). The reaction mixture was stirred under nitrogen at room temperature overnight, then was filtered, and concentrated. The residue was dissolved in 25 mL of 2:1 (v/v) ethanol:methanol and was treated with sodium borohydride (1.51 g, 39.84 mmol) in portions added over 1 hr. The reaction mixture was stirred at room temperature for 2 hr. at which time it was concentrated to one-half of its original volume. To this mixture was added 25 mL water and 25 mL saturated aqueous sodium bicarbonate. The mixture was extracted with methylene chloride and the organic layer was dried (magnesium sulfate), filtered, and concentrated. Medium pressure silica gel chromatography of the residue (methylene chloride to 10% methanol/methylene chloride) afforded 2.04 g (71%) of the title compound. MS 431.1 (M+1)+

Workup

  1. filtrationwas filtered
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in 25 mL of 2:1 (v/v) ethanol
  4. additionadded over 1 hr
  5. stirringThe reaction mixture was stirred at room temperature for 2 hr
  6. concentrationat which time it was concentrated to one-half of its original volume
  7. additionTo this mixture was added 25 mL water and 25 mL saturated aqueous sodium bicarbonate
  8. extractionThe mixture was extracted with methylene chloride
  9. dry with materialthe organic layer was dried (magnesium sulfate)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-c64c777568bc45e1961798c263bc79b1
Source dataset
uspto-grants-2006_05
Patent number
US07053212B2

Reaction notes

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