Acetonitrile → 6-Bromo-8-[(cyclopropyl-amino)-methyl]-2,2,4,4-tetramethyl-chroman

HRID 1765709Notes

Reaction equation

HRID 1765709 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH:12]=O)[CH:11]=1)[O:8][C:7]([CH3:15])([CH3:14])[CH2:6][C:5]2([CH3:17])[CH3:16].C(#N)C.[CH:21]1([NH2:24])[CH2:23][CH2:22]1.C([BH3-])#N.[Na+]>ClCCl.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH2:12][NH:24][CH:21]3[CH2:23][CH2:22]3)[CH:11]=1)[O:8][C:7]([CH3:15])([CH3:14])[CH2:6][C:5]2([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 225689466-Bromo-2,2,4,4-tetramethyl chroman-8-carbaldehyde

Product 1

HCID 211072186-Bromo-8-[(cyclopropyl-amino)-methyl]-2,2,4,4-tetramethyl-chromanYield 50%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A stirred, cooled (ice bath) solution of 6-bromo-2,2,4,4-tetramethyl chroman-8-carbaldehyde (U.S. Pat. No. 6,252,090, 2.4 g, 8.4 mmol) in dichloromethane (10 mL) and acetonitrile (9 mL) was treated with cyclopropyl amine (1.45 mL, 21 mmol). After 5 minutes, acetic acid (1 mL) was added followed by sodium cyanoborohydride (1.33 g, 21 mmol). The reaction mixture was stirred at ambient temperature for 2 h. The volatiles were distilled off in vacuo, the residue was diluted with water and extracted with ethyl acetate (×2). The combined organic extract was washed with water, saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to an oil. Flash column chromatography over silica gel (230–400 mesh) afforded the title compound (1.4 g, 50%) as a clear oil.

Workup

  1. distillationThe volatiles were distilled off in vacuo
  2. additionthe residue was diluted with water
  3. extractionextracted with ethyl acetate (×2)
  4. extractionThe combined organic extract
  5. washwas washed with water, saturated aqueous sodium bicarbonate and brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated in vacuo to an oil

Sources & evidence

ORD record
ord-ed069717ca284564870253a7aeef9d85
Source dataset
uspto-grants-2007_06
Patent number
US07226951B2

Reaction notes

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