Ethyl Acetate → methyl 6-chloro-5-{4-[(2S)-pyrrolidin-2-ylmethoxy]phenyl}-1H-indole-3-carboxylate

HRID 1054679Notes

Reaction equation

HRID 1054679 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1B1OCC(C)(C)CO1.Br[C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C@@H:30]2[CH2:34][CH2:33][CH2:32][NH:31]2)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([O:13][CH3:14])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:24]1[CH:36]=[CH:35][C:27]([O:28][CH2:29][C@@H:30]2[CH2:34][CH2:33][CH2:32][NH:31]2)=[CH:26][CH:25]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 28750222(2S)-2-[(4-Bromophenoxy)methyl]pyrrolidineHCID 86698665methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate

Product 1

HCID 86698682methyl 6-chloro-5-{4-[(2S)-pyrrolidin-2-ylmethoxy]phenyl}-1H-indole-3-carboxylateYield 71.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of methyl 6-chloro-5-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-1H-indole-3-carboxylate (80 mg, 0.146 mmol), (S)-2-((4-bromophenoxy)methyl)pyrrolidine (77 mg, 0.3 mmol), 2.0 M aqueous potassium carbonate (0.5 mL, 1.0 mmol), and Pd(dppf)Cl2 (10 mg, 0.01 mmol) in toluene/ethanol (1.44 mL/0.48 mL) was stirred at 110° C. for 2.5 hours. The mixture was poured into ethyl acetate and washed with water. The organic phase was dried over sodium sulfate, filtered, and concentrated to give a residue, which was purified by preparative TLC to give the title compound (40 mg, 42% yield) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.92 (s, 1 H), 7.80 (s, 1 H), 7.55 (s, 1 H), 7.45 (d, 2 H), 6.85 (d, 2 H), 4.10 (m, 1 H), 3.75 (s, 3 H), 3.65 (m, 1 H), 3.52 (m, 1 H), 3.05 (m, 2 H), 2.05 (m, 1 H), 1.90 (m, 2 H), 1.70 (m, 1 H).

Workup

  1. washwashed with water
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a residue, which
  6. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-ff3fd52233324edb8c5769fd8d8d1a3a
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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