Ammonia → 6-Nitro-1,2,3,4-tetrahydroisoquinoline

HRID 580940Notes

Reaction equation

HRID 580940 reaction equation
CS(Cl)(=O)=O.O[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][C:9]=1[CH2:17][CH2:18]O.C([N:22](CC)CC)C.N>C(Cl)Cl.C1COCC1.C1(C)C=CC=CC=1>[N+:14]([C:11]1[CH:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[CH2:7][NH:22][CH2:18][CH2:17]2)([O-:16])=[O:15]

Participants

8

Reactant 4

HCID 222AmmoniaHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 107265862-(2-(Hydroxymethyl)-5-nitrophenyl)ethanol

Product 1

HCID 107024586-Nitro-1,2,3,4-tetrahydroisoquinolineYield 79.8%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
24 °C

Procedure

Methanesulfonyl chloride (0.9 mL, 11.63 mmol) was added dropwise over 10 min to a solution of 2-(2-hydroxymethyl-5-nitrophenyl)-ethanol (1.0 g, 5.07 mmol), triethyl amine (1.8 mL, 12.91 mmol), in methylene chloride (20 mL). TLC showed complete reaction after 30 min. 1H NMR (CD3Cl) δ 8.17-11 (m, 2H), 7.65 (d, J=9 Hz, 1H), (s, 2H), 4.49 (t, J=6 Hz, 2H), 3.25 (t, J=6 Hz, 2H), 3.08 (s, 3H), 2.98 (s, 3H). reaction mixture was washed with 10% aqueous HCL, saturated aqueous sodium bicarbonate, and brine. The organic layer was dried with magnesium sulfate, methylene chloride removed under vacuum and chased with THF (3×100 mL). The product 1.9 g was employed directly in the next reaction without further purification. Ammonia (50 mL) was added to the dimesylate (1.9 g) in THF (30 mL) at -78° C. The contents were warmed to 24° C. for 60 hrs, ammonia distilled out, and solvent removed under vacuum to give the crude product (786 mg, 82%). Toluene was added and the solution was filtered through magnesium sulfate, and solvent removed under vacuum to yield 721 mg (75%) of an amber oil.

Workup

  1. customreaction after 30 min
  2. customreaction mixture
  3. washwas washed with 10% aqueous HCL, saturated aqueous sodium bicarbonate, and brine
  4. dry with materialThe organic layer was dried with magnesium sulfate, methylene chloride
  5. customremoved under vacuum and chased with THF (3×100 mL)
  6. customThe product 1.9 g was employed directly in the next reaction without further purification
  7. distillationammonia distilled out
  8. customsolvent removed under vacuum
  9. customto give the crude product (786 mg, 82%)
  10. filtrationthe solution was filtered through magnesium sulfate, and solvent
  11. customremoved under vacuum

Sources & evidence

ORD record
ord-6101b845f3e14ca9b297d6c6371e12be
Source dataset
uspto-grants-1999_07
Patent number
US05919795

Reaction notes

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