Sodium Bicarbonate → HCID 67224828, compound

HRID 1963980Notes

Reaction equation

HRID 1963980 reaction equation
BrC1C=CC([C:8]2([C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[NH:12][CH:11]=[CH:10][S:9]2)=CC=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][C:36]([C:39]3[NH:43][C:42]([C@@H:44]4[CH2:48][CH2:47][CH2:46][N:45]4[C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])=[N:41][CH:40]=3)=[CH:35][CH:34]=2)O1.C(=O)(O)[O-].[Na+]>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]>[C:52]([O:51][C:49]([N:45]1[CH2:46][CH2:47][CH2:48][C@H:44]1[C:42]1[NH:43][C:39]([C:36]2[CH:37]=[CH:38][C:33]([C:33]3[CH:38]=[CH:37][C:36]([C:11]4[N:12]=[C:8]([C@@H:13]5[CH2:17][CH2:16][CH2:15][N:14]5[C:18]([O:20][C:21]([CH3:22])([CH3:23])[CH3:24])=[O:19])[S:9][CH:10]=4)=[CH:35][CH:34]=3)=[CH:34][CH:35]=2)=[CH:40][N:41]=1)=[O:50])([CH3:54])([CH3:55])[CH3:53]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 56605289(s)-tert-Butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1h-imidazol-2-yl)pyrrolidine-1-carboxylate2×HCID 67223699HCID 67223699, compound

Product 1

HCID 67224828HCID 67224828, compoundYield 117.2%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
80 °C

Procedure

A flask charged with Compound 12a (0.46 g, 1.13 mmol), (S)-tert-butyl 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (compound 20a, 0.55 g, 1.25 mmol), PdCl2(dppf) (0.036 g, 0.04 mmol), and sodium bicarbonate (0.33 g, 3.93 mmol) was flushed with nitrogen, then 1,2-dimethoxyethane (6 ml) and distilled water (2 ml) were added as solvent. The reaction mixture was stirred at 80° C. under nitrogen for 5 hours. After cooled to room temperature, the mixture was extracted with ethyl acetate/water, dried over magnesium sulfate, filtered, and then concentrated to give crude compound. The crude compound was purified by column chromatography (ethyl acetate: n-hexane=4:1) to yield a yellow solid (0.47 g).

Workup

  1. customwas flushed with nitrogen
  2. distillation1,2-dimethoxyethane (6 ml) and distilled water (2 ml)
  3. additionwere added as solvent
  4. temperatureAfter cooled to room temperature
  5. extractionthe mixture was extracted with ethyl acetate/water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give crude compound
  10. customThe crude compound was purified by column chromatography (ethyl acetate: n-hexane=4:1)

Sources & evidence

ORD record
ord-fdf56b363adc48a98d1361bf7b98c0d0
Source dataset
uspto-grants-2013_04
Patent number
US08415482B2

Reaction notes

Loading…