Tetrahydrofuran → HCID 68512791, compound

HRID 1621998Notes

Reaction equation

HRID 1621998 reaction equation
[F:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][C@H:11]2[CH3:23])[CH3:9])=[CH:4][CH:3]=1.O1CCCC1.C([Li])CCC.[B:34](OC(C)C)([O:39]C(C)C)[O:35]C(C)C.[OH-].[Na+]>>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][N:10]([CH:8]([C:5]2[CH:4]=[C:3]([B:34]([OH:39])[OH:35])[C:2]([F:1])=[N:7][CH:6]=2)[CH3:9])[C@H:11]([CH3:23])[CH2:12]1)=[O:17])([CH3:21])([CH3:20])[CH3:22]

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 21531Triisopropyl borateHCID 68512865HCID 68512865, compoundHCID 178418339Butyllithium

Product 1

HCID 68512791HCID 68512791, compoundYield 73.4%

Conditions

Temperature
-78 °C

Procedure

To a 150-mL round-bottomed flask was added (3R)-tert-butyl 4-(1-(6-fluoropyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (3.0 g, 9.28 mmol), and tetrahydrofuran (100 mL, 9.28 mmol). The solution was stirred at −78° C. and treated dropwise via syringe with butyllithium solution, 2.5 m in hexanes (4.08 mL, 10.20 mmol) (Aldrich). The solution was stirred at −78° C. for 1 hr and treated in one portion with triisopropyl borate (2.55 mL, 11.13 mmol) (Aldrich). The mixture was stirred at −78° C. for 1 hour. NaOH (1.0N (30 mL) was added and the solution was stirred at room temperature for 30 minutes. The aqueous layer was separated and the organic layer was extracted with additional NaOH (1.0N, 30 mL). The combined aqueous layer was carefully acidified with 5N HCl (12 mL) to a final pH of about 4 to 5. The reaction mixture was extracted with EtOAc (3×100 mL) and the organic extract was dried over sodium sulfate, filtered and concentrated under a vacuum to give 5-(1-((R)-4-(tert-butoxycarbonyl)-2-methylpiperazin-1-yl)ethyl)-2-fluoropyridin-3-ylboronic acid (2.5 g, 6.81 mmol, 73.4% yield).

Workup

  1. stirringThe solution was stirred at −78° C. for 1 hr
  2. stirringThe mixture was stirred at −78° C. for 1 hour
  3. stirringthe solution was stirred at room temperature for 30 minutes
  4. customThe aqueous layer was separated
  5. extractionthe organic layer was extracted with additional NaOH (1.0N, 30 mL)
  6. extractionThe reaction mixture was extracted with EtOAc (3×100 mL)
  7. extractionthe organic extract
  8. dry with materialwas dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under a vacuum

Sources & evidence

ORD record
ord-742ef2191d0b4aba91b9c44f0489d3de
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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