N,N,N',N'-Tetramethylethylenediamine → {4-[(tert-Butoxycarbonyl)amino]pyridin-3-yl}boronic acid

HRID 1920253Notes

Reaction equation

HRID 1920253 reaction equation
C([Li])CCC.CCCCCC.[N:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[CH:14][CH:13]=1.CN(C)CCN(C)C.[B:34](OC)([O:37]C)[O:35]C.[Cl-].[NH4+]>O1CCCC1>[C:21]([O:20][C:19]([NH:18][C:15]1[CH:14]=[CH:13][N:12]=[CH:17][C:16]=1[B:34]([OH:37])[OH:35])=[O:25])([CH3:22])([CH3:24])[CH3:23]

Participants

8

Reactant 6

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 8058HexaneHCID 8470Trimethyl borateHCID 25517Ammonium ChlorideHCID 99902104-(Boc-amino)pyridine2×HCID 178418339Butyllithium

Product 1

HCID 46739098{4-[(tert-Butoxycarbonyl)amino]pyridin-3-yl}boronic acidYield 71.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Under a nitrogen atmosphere, a solution of n-butyllithium in hexane (100 mL of 2.5 M, 250 mmol) was added over 20 minutes to a stirred solution of tert-butyl pyridin-4-ylcarbamate (19.4 g, 100 mmol) and N,N,N′,N′-tetramethylethylenediamine (TMEDA) (31.4 g, 270 mmol) in tetrahydrofuran (THF) (500 mL) at −78° C. tert-Butyl pyridin-4-ylcarbamate is available from a literature procedure (Spivey, A. C. et al. J. Org. Chem. 1999, 64, 9430-9443). A white solid appeared and the mixture was stirred for 10 minutes at −78° C., was transferred to a salt bath, and allowed to warm slowly to −4° C. over about two hours before cooling to −78° C. again. Trimethyl borate (39.5 g, 380 mmol) was added over 15 minutes. The solution was warmed to 0° C. and poured into saturated aqueous ammonium chloride (500 mL). The mixture was stirred for 2 minutes. After standing at room temperature overnight, the mixture was partitioned between diethyl ether and brine. The organic layer was separated and washed with brine and then diluted to a volume of 3 liters with the addition of diethyl ether. A white solid formed in the organic layer and was isolated by filtration. The solid was washed sequentially with diethyl ether, water, and diethyl ether, then was dried to provide 17.1 g of 4-[(tert-butoxycarbonyl)amino]pyridin-3-ylboronic acid as a white solid.

Workup

  1. customwas transferred to a salt bath
  2. temperatureto warm slowly to −4° C. over about two hours
  3. temperaturebefore cooling to −78° C. again
  4. temperatureThe solution was warmed to 0° C.
  5. stirringThe mixture was stirred for 2 minutes
  6. waitAfter standing at room temperature overnight
  7. customthe mixture was partitioned between diethyl ether and brine
  8. customThe organic layer was separated
  9. washwashed with brine
  10. additiondiluted to a volume of 3 liters with the addition of diethyl ether
  11. customA white solid formed in the organic layer
  12. customwas isolated by filtration
  13. washThe solid was washed sequentially with diethyl ether, water, and diethyl ether
  14. customwas dried

Sources & evidence

ORD record
ord-6d652faf91f04400bd63adfdc821f1c2
Source dataset
uspto-grants-2012_05
Patent number
US08168802B2

Reaction notes

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