Hydrochloric Acid → tert-butyl 3-(5-bromo-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate

HRID 1481732Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[C:9]#[C:10][CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]1.[CH3:23]C([O-])(C)C.[K+].CI.Cl>CN1C(=O)CCC1.O>[Br:8][C:5]1[CH:4]=[C:3]2[C:2](=[CH:7][CH:6]=1)[N:1]([CH3:23])[C:10]([CH:11]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]1)=[CH:9]2

Participants

Conditions

Temperature: 780 °C

Procedure

To degassed with argon solution of tert-butyl 3-((2-amino-5-bromophenyl)ethynyl)pyrrolidine-1-carboxylate (5.69 g, 15.58 mmol) in NMP (30 mL) was added t-BuOK (3.9 g, 34.75 mmol). Mixture was heated at 780° C. for 45 min before it was cooled to 0° C. in an ice-bath. MeI (3.0 mL, 48.08 mmol) was added dropwise and reaction was allowed to warm to room temperature and stirred 30 min. Then reaction was diluted with H2O (100 mL) and acidified with 1M aqueous HCl to pH˜2. Product was extracted with EtOAc (3×150 mL). Combined organics were washed with NaCl (aqueous saturated) and dried over Na2SO4. Upon solvent removal residue was purified by column chromatography using EtOAc/hexanes (gradient 0-40%) to afford tert-butyl 3-(5-bromo-1-methyl-1H-indol-2-yl)pyrrolidine-1-carboxylate (5.17 g) in 87% yield.

Workup

temperaturewas cooled to 0° C. in an ice-bath
customreaction
temperatureto warm to room temperature
customThen reaction
extractionProduct was extracted with EtOAc (3×150 mL)
washCombined organics were washed with NaCl (aqueous saturated)
dry with materialdried over Na2SO4
customUpon solvent removal residue
customwas purified by column chromatography

Sources & evidence

ORD record: ord-dfaf359b17dc4ddeab2026575f785e5a
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409905B2

Reaction notes

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