Hydrochloric Acid → N-[(5S)-3-chloro-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide

HRID 720958Notes

Reaction equation

HRID 720958 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[C:14]([O:16][CH3:17])=[CH:15][C:10]=3[CH2:9][CH2:8][C@H:7]([NH:22][C:23](=[O:25])[CH3:24])[C:6]=2[CH:26]=1.N([O-])=O.[Na+].[ClH:31]>C(O)C.O.[Cu]Cl>[Cl:31][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[C:14]([O:16][CH3:17])=[CH:15][C:10]=3[CH2:9][CH2:8][C@H:7]([NH:22][C:23](=[O:25])[CH3:24])[C:6]=2[CH:26]=1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid3×HCID 23668193Sodium NitriteHCID 57174210N-[(5S)-3-amino-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide

Product 1

HCID 58658620N-[(5S)-3-chloro-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamideYield 46%

Reagents, catalysts & solvents 3

HCID 62652Cuprous chlorideCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of N-[(5S)-3-amino-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide (0.712 g; 2 mmol) in ethanol (3.75 ml) and 36% hydrochloric acid (1.57 ml) was slowly added into a mixture of ice (6 ml) and 36% hydrochloric acid (1.57 ml). At 0° C. a solution of sodium nitrite (0.14 g; 2 mmol) in water (0.25 ml) was added. The mixture was stirred at 0° C. for 1 hour and then transferred into a separate flask containing a solution of copper(I) chloride (0.218 g; 2.2 mmol) in water (0.35 ml) and 36% hydrochloric acid (0.4 ml). The resulting mixture was stirred at 30° C. for 30 minutes and extracted with toluene/ethyl acetate (50/50). The organic phase was washed with water, dilute sodium hydroxide, and saturated sodium chloride solution, then dried and the volatiles were removed by evaporation. The residue was purified by flash chromatography eluting with ethyl acetate to give N-[(5S)-3-chloro-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide.

Workup

  1. customtransferred into a separate flask
  2. stirringThe resulting mixture was stirred at 30° C. for 30 minutes
  3. extractionextracted with toluene/ethyl acetate (50/50)
  4. washThe organic phase was washed with water, dilute sodium hydroxide, and saturated sodium chloride solution
  5. customdried
  6. customthe volatiles were removed by evaporation
  7. customThe residue was purified by flash chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-135ca31d2cfd46ba95a77cebd2774b9c
Source dataset
uspto-grants-2006_11
Patent number
US07135502B1

Reaction notes

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