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

HRID 1056653Notes

Reaction equation

HRID 1056653 reaction equation
O1C[CH2:4][CH2:3][CH2:2]1.[CH2:6]1[C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:12][C:11]=2[CH:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9][NH:8][CH2:7]1.C(=O)([O-])[O-].[K+].[K+].C(Br)C=C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCO.C(Cl)Cl>[CH2:4]([N:8]1[CH2:7][CH2:6][C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[NH:12][C:11]=2[CH:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1)[CH:3]=[CH2:2]

Participants

7

Reactant 4

HCID 7841Allyl bromideHCID 8028TetrahydrofuranHCID 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-carboxylate

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 21584144Dichloromethane ethanolSolvent

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, 0.06mol), 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
  10. customYield =83%

Sources & evidence

ORD record
ord-3d54ced894b64f29b0df489f300d2f8d
Source dataset
uspto-grants-2016_07
Patent number
US09399642B2

Reaction notes

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