Triethylamine → ethyl (4aS,9bR)-6-bromo-1H,2H,3H,4H,4aH,5H,9bH-pyrido(4,3-b)indole-2-carboxylate

HRID 1624922Notes

Reaction equation

HRID 1624922 reaction equation
[OH-].[Na+].[Br:3][C:4]1[C:12]2[NH:11][C@H:10]3[CH2:13][CH2:14][NH:15][CH2:16][C@H:9]3[C:8]=2[CH:7]=[CH:6][CH:5]=1.C(N(CC)CC)C.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26]>C1COCC1>[Br:3][C:4]1[C:12]2[NH:11][C@H:10]3[CH2:13][CH2:14][N:15]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:16][C@H:9]3[C:8]=2[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 59317963(4aS,9bR)-6-Bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 59317960ethyl (4aS,9bR)-6-bromo-1H,2H,3H,4H,4aH,5H,9bH-pyrido(4,3-b)indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate may be prepared by first obtaining [4aS,9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (36.0 g, 0.142 mol)) as a free base by using 50% aqueous sodium hydroxide solution and extracting the product into MTBE. The conversion to (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate may then be done by cooling a suspension of compounds of [4aS,9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (36.0 g, 0.142 mol)) in THF (300 ml) and triethylamine (24 ml) in an ice-water bath. Ethyl chloroformate is added dropwise (13.5 ml, 0.142 mol) via a syringe pump over 1 hour. The ice-water bath is removed and the reaction mixture is stirred at room temperature for another hour. The reaction mixture is passed through a pad of celite and the solvent is evaporated to give (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate). 1H NMR (CDCl3, 300 MHz): 1.20-1.35 (m, 3H), 1.73-1.85 (m, 1H), 1.85-1.99 (m, 1H), 3.22-3.52 (m, 3H), 3.52-3.66 (m, 1H), 3.66-3.95 (Br, 1H), 3.95-4.21 (m, 4H), 6.60 (t, J=7.7 Hz, 1H), 7.04 (d, J=7.2 Hz, 1H), 7.20 (d, J=8.1 Hz, 1H).

Workup

  1. extractionextracting the product into MTBE
  2. temperatureby cooling
  3. customThe ice-water bath is removed
  4. customthe solvent is evaporated

Sources & evidence

ORD record
ord-029d32b8bb4c44f3abac152b7407531e
Source dataset
uspto-grants-2014_07
Patent number
US08779139B2

Reaction notes

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