Sodium → 7-Methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine

HRID 1040603Notes

Reaction equation

HRID 1040603 reaction equation
[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]2[CH2:7][CH2:8][N:9](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:10][CH2:11][C:5]=2[CH:4]=1.C(=O)=O.CC(C)=O.[Na]>N>[CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]2[CH2:7][CH2:8][NH:9][CH2:10][CH2:11][C:5]=2[CH:4]=1

Participants

5

Reactant 3

HCID 5360545SodiumHCID 18522661Acetone cardiceHCID 222509407-methoxy-3-(toluene-4-sulfonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 138533487-Methoxy-2,3,4,5-tetrahydro-1h-3-benzazepine

Reagents, catalysts & solvents 1

HCID 222AmmoniaSolvent

Procedure

7-Methoxy-3-(toluene-4-sulfonyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (3.9 g/11.8 mmol) was placed in a round bottom flask and cooled to −78 C (external CO2/acetone bath). Ammonia (ca. 20 mL) was condensed into the flask and freshly cut sodium (3 g) was carefully added in small pieces (dark blue color observed) and the reaction allowed to stir for one hour. The reaction was quenched by the addition of solid ammonium chloride followed by careful addition of diethyl ether (30 mL). The reaction was then allowed to warm to room temperature and the ammonia allowed to boil off. Water was then carefully added (50 mL) and the layers separated. The organic layer was extracted with 1 N hydrochloric acid (2×50 mL). The aqueous extracts were basified with 33% aqueous sodium hydroxide and extracted with 10% methanol/methylene chloride (3×50 mL). The combined organic extracts were dried (magnesium sulfate), filtered and concentrated to afford 7-Methoxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a colorless oil (1.7 g/81%). 1H NMR (400 MHz, CDCl3) δ 7.02 (d, J=8.0 Hz, 1H), 6.68-6.61 (m, 2H), 3.81 (s, 3 H), 2.99-2.82 (m, 8H).

Workup

  1. additionwas carefully added in small pieces (dark blue color observed)
  2. customThe reaction was quenched by the addition of solid ammonium chloride
  3. additionfollowed by careful addition of diethyl ether (30 mL)
  4. additionWater was then carefully added (50 mL)
  5. customthe layers separated
  6. extractionThe organic layer was extracted with 1 N hydrochloric acid (2×50 mL)
  7. extractionextracted with 10% methanol/methylene chloride (3×50 mL)
  8. dry with materialThe combined organic extracts were dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-bc4ee640429d4ae6907fa28d18e87f18
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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