Ammonia → 3,4-Dihydro-2H-1-benzopyran-4-amine

HRID 1910609Notes

Reaction equation

HRID 1910609 reaction equation
[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=O)[CH2:3][CH2:2]1.[NH3:12].C(O)C.[BH4-].[Na+]>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[O:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([NH2:12])[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 702EthanolHCID 68110ChromanoneHCID 4311764Sodium borohydride

Product 1

HCID 49619573,4-Dihydro-2H-1-benzopyran-4-amineYield 87%

Reagents, catalysts & solvents 1

HCID 11026Titanium isopropoxideCatalyst

Conditions

Temperature
0 °C

Procedure

Chroman-4-one (3 g, 20.1 mmol), titanium(IV) isopropoxide (12.0 mL, 40.2 mmol) and 2 M solution of ammonia in ethanol (60.6 mL, 121.2 mmol) were stirred at room temperature for 6 h. The reaction was cooled to 0° C. and sodium borohydride was added portionwise during 10 min (1.14 g, 30.2 mmol); the resultant mixture was stirred at rt for an additional 3 h. The reaction was quenched by pouring it into ammonium hydroxide (2 M, 60 mL), the precipitate that formed was filtered off and washed with ethyl acetate (15 mL×3). The organic layer was separated and the remaining aqueous layer was extracted with ethyl acetate (15 mL×2). The combined organic extracts were washed with 1 M HCl (25 mL). The acidic aqueous extracts were washed with ethyl acetate (50 mL), then treated with aqueous sodium hydroxide (2 M) to pH 10-12, and extracted with ethyl acetate (40 mL×3). The combined organic extracts were washed with brine, dried (Na2SO4), and concentrated in vacuo to afford Chroman-4-amine as an oil (2.61 g, 87% yield). 1H NMR (400 MHz, CDCl3) δ 7.31 (d, 1H), 7.23 (m, 1H), 6.94 (m, 1H), 6.82 (d, 1H), 4.38 (m, 2H), 4.12 (m, 1H), 2.19 (m, 2H), 1.82 (m, 2H).

Workup

  1. customThe reaction was quenched
  2. additionby pouring it into ammonium hydroxide (2 M, 60 mL)
  3. customthe precipitate that formed
  4. filtrationwas filtered off
  5. washwashed with ethyl acetate (15 mL×3)
  6. customThe organic layer was separated
  7. extractionthe remaining aqueous layer was extracted with ethyl acetate (15 mL×2)
  8. washThe combined organic extracts were washed with 1 M HCl (25 mL)
  9. washThe acidic aqueous extracts were washed with ethyl acetate (50 mL)
  10. additiontreated with aqueous sodium hydroxide (2 M) to pH 10-12
  11. extractionextracted with ethyl acetate (40 mL×3)
  12. washThe combined organic extracts were washed with brine
  13. dry with materialdried (Na2SO4)
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e14c60adcd0d4eec80ff7a666ce8dacc
Source dataset
uspto-grants-2013_12
Patent number
US08604021B2

Reaction notes

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