Hydrochloric Acid → 1-(tert-Butoxycarbonyl)-2-pyrroleboronic Acid

HRID 857161

Reaction equation

HRID 857161 reaction equation
C([Li])[CH2:2][CH2:3][CH3:4].[C:6]([N:13]1[CH:17]=[CH:16][CH:15]=[CH:14]1)([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[B:18](OC)([O:21]C)[O:19][CH3:20].Cl>C1COCC1>[CH:3]([NH:13][CH:17]([CH3:16])[CH3:20])([CH3:4])[CH3:2].[C:9]([O:8][C:6]([N:13]1[CH:14]=[CH:15][CH:16]=[C:17]1[B:18]([OH:21])[OH:19])=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8470Trimethyl borateHCID 643494tert-butyl 1H-pyrrole-1-carboxylateHCID 178418339Butyllithium

Product 2

HCID 7912DiisopropylamineHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of anhydrous diisopropylamine (3.35 mL, 23.9 mmol) was prepared in 100 mL of anhydrous THF and cooled at −78° C. A solution of 2.5 M of n-butyllithium (10.5 mL, 26.3 mmol) was slowly added to the THF solution over 10 minutes. The resulting mixture was stirred at −78° C. for 15 minutes and was then warmed to 0° C. for 15 minutes. The resulting mixture was cooled again at −78° C. and the tert-butyl 1-pyrrole carboxylate (73) (4.00 mL, 23.9 mmol) was added. The resulting solution was stirred for 1 hour at −78° C. and trimethyl borate (2.70 mL, 23.9 mmol) was added. The resulting solution was allowed to warm up to room temperature overnight. 20 mL of dilute HCl (0.25N) was added to the room temperature solution, which was stirred at room temperature for 15 minutes. The THF was removed under reduced pressure. The residue was extracted with diethyl ether (3×100 mL). The organic layer was dried over sodium sulfate, filtered and then concentrated in vacuo. Trituration with hexane (10 mL) and filtration gave the Compound 8 as beige solid (2.56 g, 51%). 1H NMR (500 MHz, CDCl3): δ (ppm), 7.71 (s, 2H); 7.48 (t, 1H, J=2 Hz); 7.15 (t, 1H, J=1.8 Hz); 6.29 (t, 1H, J=3.1 Hz); 1.65 (3, 9H). 13C NMR (500 MHz, CDCl3): δ (ppm), 153.22; 129.67; 127.92; 112.96; 86.47; 28.84.

Workup

  1. temperaturewas then warmed to 0° C. for 15 minutes
  2. temperatureThe resulting mixture was cooled again at −78° C.
  3. stirringThe resulting solution was stirred for 1 hour at −78° C.
  4. temperatureto warm up to room temperature overnight
  5. stirringwas stirred at room temperature for 15 minutes
  6. customThe THF was removed under reduced pressure
  7. extractionThe residue was extracted with diethyl ether (3×100 mL)
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. filtrationTrituration with hexane (10 mL) and filtration

Sources & evidence

ORD record
ord-fb1eb7d6f0a742ed82b0338b85f956d5
Source dataset
uspto-grants-2006_12
Patent number
US07144912B2

Linked notes

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