Allyl bromide → Methyl 3-allyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate

HRID 1056654Notes

Reaction equation

HRID 1056654 reaction equation
[CH2:1]1[C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4][NH:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:25](Br)[CH:26]=[CH2:27]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>[CH2:27]([N:3]1[CH2:2][CH2:1][C:14]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[NH:7][C:6]=2[CH:5]([C:15]([O:17][CH3:18])=[O:16])[CH2:4]1)[CH:26]=[CH2:25]

Participants

6

Reactant 3

HCID 7841Allyl bromideHCID 11430Potassium CarbonateHCID 11021133Methyl 1,2,3,4,5,6-hexahydroazepino(4,5-b)indole-5-carboxylate

Product 1

HCID 11300600Methyl 3-allyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylateYield 83%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A 72 L three-necked mechanically stirred round bottomed flask was set up with a reflux condenser. To the flask was charged dry tetrahydrofuran (10 L), and methyl 1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate (800 g, 3.27 mol). The mixture was stirred, and tetrabutylammonium bromide (21.1 g, 0.06 mol), anhydrous potassium carbonate (1.13 kg, 8.8 mol), and allyl bromide (29.7 mL, 396 g, 3.27 mol) were added sequentially in one lot each. After addition, the mixture was stirred at about 20° C. for 2.5 days. The mixture was diluted with (10 L) hexanes, filtered, and transferred to a separatory funnel. The solution was washed with water (2 L), saturated sodium chloride (1 L), dried over sodium sulfate, filtered, then concentrated to a dark green-brown oil (770 g), methyl 3-allyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate, suitably clean to be used in the next synthetic step. Yield=83%. TLC (EtOH/CH2Cl2, 1:9): Rf=0.7; 1H NMR (400 MHz, CDCl3): δ 2.79-2.86 (m, 1H), 2.90-3.09 (m, 4H), 3.28-3.43 (m, 3H), 3.78 (s, 3H), 4.02 (dd, J=1.6, 6.8 Hz, 1H), 5.23 (d, J=10.4 Hz, 1H), 5.27 (dd, J=1.4, 17 Hz, 1H), 5.90-6.00 (m, 1H), 7.11-7.19 (m, 2H), 7.29 (d, J=7.6 Hz, 1H), 7.53 (d, J=7.2 Hz, 1H), 8.40 (bs, 1H); 13C NMR (100 MHz, CDCl3): δ 24.1, 45.4, 52.2, 55.7, 56.9, 61.4, 110.7, 113.8, 117.5, 118.0, 119.2, 121.4, 128.4, 132.1, 134.7, 135.7, 172.5; melting point: 105-108° C. (uncorrected).

Workup

  1. customA 72 L three-necked mechanically stirred round bottomed flask was set up with a reflux condenser
  2. additionAfter addition
  3. stirringthe mixture was stirred at about 20° C. for 2.5 days
  4. filtrationfiltered
  5. customtransferred to a separatory funnel
  6. washThe solution was washed with water (2 L), saturated sodium chloride (1 L)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a dark green-brown oil (770 g), methyl 3-allyl-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole-5-carboxylate

Sources & evidence

ORD record
ord-9a7688c213714f649294635dfc70377a
Source dataset
uspto-grants-2016_07
Patent number
US09399643B2

Reaction notes

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