tert-Butanol → Tert-butyl (6-bromo-5-fluoropyridin-2-YL)carbamate

HRID 1396477Notes

Reaction equation

HRID 1396477 reaction equation
[Br:1][C:2]1[N:7]=[C:6](C(O)=O)[CH:5]=[CH:4][C:3]=1[F:11].C([N:14]([CH2:17]C)CC)C.C1C=CC(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:26])=CC=1.[C:36]([OH:40])([CH3:39])([CH3:38])[CH3:37]>>[C:36]([O:40][C:17](=[O:26])[NH:14][C:6]1[CH:5]=[CH:4][C:3]([F:11])=[C:2]([Br:1])[N:7]=1)([CH3:39])([CH3:38])[CH3:37]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 534011946-Bromo-5-fluoropicolinic Acid

Product 1

HCID 71744124Tert-butyl (6-bromo-5-fluoropyridin-2-YL)carbamateYield 59%

Procedure

To a solution of 6-bromo-5-fluoro-2-picolinic acid (2 g, 9.09 mmol) in tert-butanol (46 mL) and triethylamine (1.27 mL, 9.09 mmol, Eq: 1.00) was added DPPA (1.97 mL, 9.09 mmol). The slurry was stirred at room temperature until all solids dissolved (˜15 min), after which it was heated to 85° C. for 2 h. Upon cooling the mixture was concentrated onto silica gel and chromatographed (silica, 5% to 30% EtOAc in hexanes) to give slightly impure (6-bromo-5-fluoro-pyridin-2-yl)-carbamic acid tert-butyl ester (1.55 g, 59%). 1H NMR (400 MHz, CHLOROFORM-d6) δ ppm 7.97 (d, J=8.6 Hz, 1H), 7.43 (d, J=8.6 Hz, 1H), 1.53 (s, 9H).

Workup

  1. dissolutiondissolved (˜15 min)
  2. temperatureafter which it was heated to 85° C. for 2 h
  3. temperatureUpon cooling the mixture
  4. concentrationwas concentrated onto silica gel
  5. customchromatographed (silica, 5% to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-d04b4f50e3a2417bb48eae33e0da3e75
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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