Iodine → [5-Amino-2-(morpholin-4-yl)phenyl]methanol

HRID 589577

Reaction equation

HRID 589577 reaction equation
[BH4-].[Na+].O1CCCC1.[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[C:13]([C:15](O)=[O:16])[CH:14]=1.II>CO>[NH2:8][C:9]1[CH:10]=[CH:11][C:12]([N:18]2[CH2:19][CH2:20][O:21][CH2:22][CH2:23]2)=[C:13]([CH:14]=1)[CH2:15][OH:16]

Participants

6

Reactant 4

HCID 807Iodine2×HCID 8028Tetrahydrofuran2×HCID 6137005-Amino-2-morpholinobenzenecarboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 23136616[5-Amino-2-(morpholin-4-yl)phenyl]methanolYield 72%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A 50 mL two necked round bottom flask was fitted with a magnetic stirrer bar and a dropping funnel. A suspension of NaBH4 in tetrahydrofuran (100 mg, 2 4 mmol/10 mL) was added, followed by 5-amino-2-morpholinobenzenecarboxylic acid (222 mg, 1.0 mmol) in one portion. A reflux condenser was fitted and the reaction mixture was cooled to 0° C. under nitrogen atmosphere. A solution of iodine in tetrahydrofuran (250 mg, 1.0 mmol/15 mL) was added dropwise to the reaction mixture. After iodine addition was completed and gas evolution had ceased, the reaction mixture was heated at reflux for 6 hours and left stirring at room temperature overnight. Methanol was added slowly until the mixture became clear. The resulting solution stirred at room temperature for 30 minutes then solvent was removed under reduced pressure. The residue was dissolved in 20% KOH (30 mL), stirred for 4 hours and extracted with dichloromethane (3×30 mL). The combined organic extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated to give 5-amino-2-morpholinobenzyl alcohol as an off-white solid (150 mg, 72% yield). 1H NMR (300 MHz, CDCl3) δ 7.05 (d, J=8.7 Hz, 1H), 6.59 (dd, J=8.4, 2.7 Hz, 1H), 6.49 (d, J=2.7 Hz, 1H), 5.51 (br s, 1H), 4.71 (s, 2H), 3.84 (t, J=5.1 Hz, 4H), 3.60 (br s, 2H), 2.91 (t, J=5.1 Hz, 4H). LC-ESI-MS (method B): rt 2.31 min.; m/z 209.2 [M+H]+.

Workup

  1. additionwas added
  2. customA reflux condenser was fitted
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 6 hours
  5. waitleft
  6. stirringThe resulting solution stirred at room temperature for 30 minutes
  7. customsolvent was removed under reduced pressure
  8. dissolutionThe residue was dissolved in 20% KOH (30 mL)
  9. stirringstirred for 4 hours
  10. extractionextracted with dichloromethane (3×30 mL)
  11. washThe combined organic extracts were washed with brine
  12. dry with materialdried over anhydrous Na2SO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-8148e650e754428f9e1352cef577fbf4
Source dataset
uspto-grants-2016_01
Patent number
US09233934B2

Linked notes

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