Toluene → 3-(5-{(S)-1-[1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-indole-1-carboxylic Acid Tert-butyl Ester

HRID 1667629Notes

Reaction equation

HRID 1667629 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C@H:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@H:12]2[C:16]2[CH:17]=[N:18][CH:19]=[C:20](B3OC(C)(C)C(C)(C)O3)[CH:21]=2)[CH3:10])=[CH:5][CH:4]=1.[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40](Br)=[CH:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>C(O)C>[C:31]([O:35][C:36]([N:38]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]([C:20]2[CH:19]=[N:18][CH:17]=[C:16]([C@@H:12]3[CH2:13][CH2:14][CH2:15][N:11]3[CH:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH3:10])[CH:21]=2)=[CH:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Participants

6

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 20097636tert-Butyl 3-bromo-1H-indole-1-carboxylateHCID 581118623-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine

Product 1

HCID 581119913-(5-{(S)-1-[1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-indole-1-carboxylic Acid Tert-butyl EsterYield 59%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 3-{(S)-1-[(R)-1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine 4 (crude, 6.93 mmole), 3-bromo-indole-1-carboxylic acid tert-butyl ester (2.46 g, 8.32 mmole), Na2CO3 (35 mL, 35 mole, 1 M aqueous) in a mixed solution of 50 mL of toluene and 20 mL of ethanol was degased under vacuum. After heat at 80° C. for 1.5 hours, the reaction mixture was cooled to room temperature and dilutied with 150 mL of EtOAc, and washed by 2×100 mL of water. The organic layer was filtered and concentrated. The crude producte was purified by flash chromatography (Hexane 70%, EtOAc 30%) to give 3-(5-{(S)-1-[1-(4-Methoxy-phenyl)-ethyl]-pyrrolidin-2-yl}-pyridin-3-yl)-indole-1-carboxylic acid tert-butyl ester 5 (2.02 g, 59% in two steps) as light brown gum.

Workup

  1. customwas degased under vacuum
  2. temperaturethe reaction mixture was cooled to room temperature
  3. washwashed by 2×100 mL of water
  4. filtrationThe organic layer was filtered
  5. concentrationconcentrated
  6. customThe crude producte was purified by flash chromatography (Hexane 70%, EtOAc 30%)

Sources & evidence

ORD record
ord-0d947461826b49888b63824f66c4dd53
Source dataset
uspto-grants-2011_10
Patent number
US08044209B2

Reaction notes

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