Hydrogen Bromide → 3-(Methyl(3-phenylpropyl)amino)-5-hydroxychroman

HRID 1684719Notes

Reaction equation

HRID 1684719 reaction equation
[NH2:1][CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[O:12]C)[O:4][CH2:3]1.C([BH3-])#N.[Na+].[C:18]1([CH2:24][CH2:25][CH:26]=O)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[CH2:28]=O.Br.[OH-].[Na+]>CO.C1(C)C=CC=CC=1.C(O)(=O)C>[CH3:28][N:1]([CH2:26][CH2:25][CH2:24][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH:2]1[CH2:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[OH:12])[O:4][CH2:3]1

Participants

10

Reactant 6

HCID 260Hydrogen BromideHCID 712FormaldehydeHCID 7707BenzenepropanalHCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydride2×HCID 139289485-Methoxy-3,4-dihydro-2H-1-benzopyran-3-amine

Product 1

HCID 190281563-(Methyl(3-phenylpropyl)amino)-5-hydroxychroman

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

3-Amino-5-methoxychroman (Thorberg et al. Acta Pharm. Suec. 24(1987)) (2.0 g, 9.28 mmol) was dissolved in methanol (50 ml) and pH was adjusted to 6.0 with acetic acid. The solution was cooled to 0° C. and sodium cyanoborohydrid (0.87 g, 13.8 mmol) was added together with 3-phenylpropanal (1.22 ml, 9.28 mmol), the cooling was withdrawn and the solution was stirred at ambient temperature for 4 hours. Paraformaldehyde (0.42 g, 14 mmol) and sodium cyanoborohydride (0.87 g, 9.28 mmol) was added and stirring was continued overnight at ambient temperature. The solution was diluted with toluene and washed with water. Drying with sodium sulfate and evaporation to dryness gives an oil. The oil was purified by flash chromatography on silica gel by elution with ethylacete/hexane 1:4. The collected fractions were evaporated to give an oil. The oil was treated with HBr (47% aq.) at 120° C. for 1 hour. The solution was cooled and neutralised with sodium hydroxide and extracted with toluene. The organic phase was dried and evaporated to give the title compound as an oil. 13C-NMR: 22.502 29.09 33.47 38.19 53.66 67.75 102.04 109.20 110.46 125.78 127.05 128.36 142.20 155.29 158.28.

Workup

  1. customthe cooling was withdrawn
  2. stirringstirring
  3. waitwas continued overnight at ambient temperature
  4. washwashed with water
  5. dry with materialDrying with sodium sulfate and evaporation to dryness
  6. customgives an oil
  7. customThe oil was purified by flash chromatography on silica gel by elution with ethylacete/hexane 1:4
  8. customThe collected fractions were evaporated
  9. customto give an oil
  10. temperatureThe solution was cooled
  11. extractionextracted with toluene
  12. customThe organic phase was dried
  13. customevaporated

Sources & evidence

ORD record
ord-d5155c5b87b04b259e4c3367e5e52701
Source dataset
uspto-grants-1997_06
Patent number
US05641807

Reaction notes

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