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

HRID 629313Notes

Reaction equation

HRID 629313 reaction equation
[Br:1][C:2]1[C:10]2[NH:9][C@H:8]3[CH2:11][CH2:12][NH:13][CH2:14][C@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([O-])(=O)[C@H](C1C=CC=CC=1)O.C([O-])([O-])=O.[Na+].[Na+].Cl[C:33]([O:35][CH2:36][CH3:37])=[O:34]>C1COCC1>[Br:1][C:2]1[C:10]2[NH:9][C@H:8]3[CH2:11][CH2:12][N:13]([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:14][C@H:7]3[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 10928Ethyl chloroformateHCID 5460348(S)-MandelateHCID 59317963(4aS,9bR)-6-Bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole3×

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 8028TetrahydrofuranSolvent2×

Conditions

Temperature
25 °C

Procedure

Alternative to the use of [4aS,9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole (Compound of Formula 1C) free base, the reaction may also be done by starting with the (S)-mandelate salt of [4aS,9bR]-6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole. A 100 mL round-bottomed flask is equipped with a magnetic stirring bar, a pressure-equalizing addition funnel, and a N2 inlet on top of the addition funnel. The flask is charged with the S-mandelate starting material (5 g, 12.35 mmol), Na2CO3 (2.88 g, 27.17 mmol), and 25 mL of THF. To the yellow reaction mixture at 25° C. (heating block temperature) is added a solution of ethyl chloroformate (1.64 g, 15.11 mmol) in 5 mL of THF dropwise over ca 70 minutes. The batch is stirred at 25° C. for another 10 min, and is checked by HPLC. Less than 2% of the starting material is observed by HPLC, and the desired product is registered at ca. 98%. To the batch is added 12.5 mL of EtOH, and the batch is concentrated under reduced pressure to remove ca. 30 mL of solvent (mostly THF). To the batch is then added 37.5 mL of H2O, and the resultant mixture shows pH>9 by pH paper. The yellow mixture is then stirred at rt for ca. 1 h, and is filtered. The solid is rinsed with 25 mL of H2O. After drying in a vacuum oven at 58° C. for ca. 16 h, 3.9442 g of a yellow solid is obtained (98% yield). 1H NMR of the solid conformed, and showed no (s)-mandelic acid. HPLC analysis of the product shows the desired product at >99% purity. LC-MS showed a peak with M/e=326 (M+1).

Workup

  1. customthe reaction
  2. customA 100 mL round-bottomed flask is equipped with a magnetic stirring bar, a pressure-equalizing addition funnel, and a N2 inlet on top of the addition funnel

Sources & evidence

ORD record
ord-41b6c2cf319c41babfe8b90e5f22dc60
Source dataset
uspto-grants-2016_04
Patent number
US09315504B2

Reaction notes

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