Acetic Acid → 6-(Methyloxy)-7-nitro-2-(1-propyl-4-piperidinyl)-1,2,3,4-tetrahydroisoquinoline

HRID 1014310Notes

Reaction equation

HRID 1014310 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][C:7](=O)[CH2:6][CH2:5]1)[CH2:2][CH3:3].[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[N+:23]([O-:25])=[O:24])[CH2:19][NH:18][CH2:17][CH2:16]2.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(N(CC)CC)C>[CH3:11][O:12][C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][C:22]=1[N+:23]([O-:25])=[O:24])[CH2:19][N:18]([CH:7]1[CH2:8][CH2:9][N:4]([CH2:1][CH2:2][CH3:3])[CH2:5][CH2:6]1)[CH2:17][CH2:16]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 900061-Propyl-4-piperidoneHCID 5049666Sodium triacetoxyborohydrideHCID 594418746-Methoxy-7-nitro-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 594416526-(Methyloxy)-7-nitro-2-(1-propyl-4-piperidinyl)-1,2,3,4-tetrahydroisoquinolineYield 89.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 1-propyl-4-piperidinone (01.25 mL, 8.3 mmol), 6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (1.0 g, 4.8 mmol), acetic acid (0.55 mL) and triethylamine (1.3 mL) in 1,2-dichloroethane (5 mL) was stirred for 30 minutes. Sodium triacetoxyborohydride (1.8 g, 2.8 mmol) was added. After stirring for 12 hours the reaction was quenched by the addition of saturated NaHCO3 (aq). The reaction was diluted with dichloromethane and the layers were separated. The aqueous phase was extracted with dichloromethane. The combined organic layers were washed with water, dried over MgSO4 and concentrated onto silica gel. The crude material was purified by flash column chromatography to give 6-(methyloxy)-7-nitro-2-(1-propyl-4-piperidinyl)-1,2,3,4-tetrahydroisoquinoline (1.43 g, 89%). 1H NMR (400 MHz, CDCl3) δ ppm 7.60 (s, 1 H), 6.78 (s, 1 H), 3.91 (s, 3 H), 3.73 (s, 2 H), 3.07 (d, J=9.17 Hz, 2 H), 2.91 (t, J=5.87 Hz, 2 H), 2.83 (t, J=5.68 Hz 2 H), 2.47-2.60 (m, 1 H), 2.29-2.42 (m, 2 H), 2.04 (d, J=10.63 Hz, 2 H), 1.68-1.94 (m, 4 H), 1.49-1.66 (m, 2 H), 0.91 (t, J=7.33 Hz, 3 H).

Workup

  1. stirringAfter stirring for 12 hours the reaction
  2. customwas quenched by the addition of saturated NaHCO3 (aq)
  3. additionThe reaction was diluted with dichloromethane
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with dichloromethane
  6. washThe combined organic layers were washed with water
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated onto silica gel
  9. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-40026031d9024d30a50a24d62fc4f167
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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