Trimethyl borate → 4-(t-Butoxycarbonylamino)naphthalene-1-boronic acid

HRID 1794671Notes

Reaction equation

HRID 1794671 reaction equation
C([Mg]Cl)CCC.C([Li])CCC.[C:12]([NH:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23](Br)=[CH:22][CH:21]=1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].[B:31](OC)([O:34]C)[O:32]C.[Cl-].[NH4+].C(=O)(O)[O-].[Na+]>C1COCC1.C(OCC)(=O)C>[C:12]([NH:19][C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([B:31]([OH:34])[OH:32])=[CH:22][CH:21]=1)([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13]

Participants

9

Reactant 6

HCID 8470Trimethyl borateHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 11602218tert-Butyl (4-bromonaphthalen-1-yl)carbamateHCID 178418265HCID 178418265, compoundHCID 178418339Butyllithium

Product 1

HCID 99712804-(t-Butoxycarbonylamino)naphthalene-1-boronic acidYield 80.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

In a dry flask under Argon was added butylmagnesium chloride (2.0 M in THF, 2.0 mL, 4.0 mmol) and anhydrous THF (10 mL). The solution was cooled to −5° C. and butyllithium (1.6 M in hexane, 5.0 mL, 8.0 mmol) was added dropwise while the temperature was kept below 0° C. After the resulting solution was stirred at 0° C. for 0.5 h, the temperature was lowered to −5° C. N-Boc-4-bromo-1-aminonaphthalene (0.64 g, 2.0 mmol) was dissolved in anhydrous THF(10 mL) and added dropwise while the temperature was kept below 0° C. The solution was stirred at 0° C. for 0.5 h. HPLC of a sample taken from the solution and quenched with MeOH indicated that no starting material was left. The temperature was lowered to −5° C. and trimethyl borate(2.5 mL, 22.0 mmol) was added slowly. After the mixture was stirred at 0° C. for 2 h, ammonium chloride solution (saturated, 20 mL) was added and the mixture was stirred at 21° C. for 0.5 h. The pH of the mixture was adjusted to 7 with sodium bicarbonate and the mixture was stirred at 21° C. for 18 h. Ethyl acetate (10 mL) was added and the mixture was stirred for 0.5 h. The organic layer was separated and dried with magnesium sulfate. The solvent was removed under vacuum and then hexane (60 mL) was added and the resulting slurry was stirred for 0.5 h. Filtration and hexane (10 mL) wash gave the title compound as a white solid (0.46 g, 80.5% pure, 65% yield).

Workup

  1. customwas kept below 0° C
  2. customwas lowered to −5° C
  3. additionadded dropwise while the temperature
  4. customwas kept below 0° C
  5. stirringThe solution was stirred at 0° C. for 0.5 h
  6. customquenched with MeOH
  7. waitwas left
  8. customwas lowered to −5° C.
  9. stirringAfter the mixture was stirred at 0° C. for 2 h
  10. stirringthe mixture was stirred at 21° C. for 0.5 h
  11. stirringthe mixture was stirred at 21° C. for 18 h
  12. stirringthe mixture was stirred for 0.5 h
  13. customThe organic layer was separated
  14. dry with materialdried with magnesium sulfate
  15. customThe solvent was removed under vacuum
  16. additionhexane (60 mL) was added
  17. stirringthe resulting slurry was stirred for 0.5 h
  18. filtrationFiltration and hexane (10 mL)
  19. washwash

Sources & evidence

ORD record
ord-a419f6318ec24697a0901335b7f7e9ef
Source dataset
uspto-grants-2006_04
Patent number
US07022883B2

Reaction notes

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