Water → tert-Butyl 2-(6-formylpyridin-2-yl)benzyl(phenyl)carbamate

HRID 1188303Notes

Reaction equation

HRID 1188303 reaction equation
O.C(=O)([O-])[O-].[Na+].[Na+].Br[C:9]1[N:14]=[C:13]([CH:15]=[O:16])[CH:12]=[CH:11][CH:10]=1.[C:17]1([N:23]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=2B2OC(C)(C)C(C)(C)O2)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1.O.CO.CO>[CH:15]([C:13]1[N:14]=[C:9]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[CH2:31][N:23]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH:10]=[CH:11][CH:12]=1)=[O:16]

Participants

8

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27570096-Bromopyridine-2-carbaldehydeHCID 66795645Tert-butyl phenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)carbamate

Product 1

HCID 58434438tert-Butyl 2-(6-formylpyridin-2-yl)benzyl(phenyl)carbamateYield 840%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of water (160 mL) and methanol (40 mL) was combined with sodium carbonate (3.80 g, 35.9 mmol), and the mixture was sparged with nitrogen for 30 min. In a separate flask were combined, under nitrogen, 6-bromo-2-pyridinecarboxaldehyde (2.67 g, 14.4 mmol), tert-butyl phenyl(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)carbamate (5.87 g, 14.4 mmol), tetrakis(triphenylphosphinio)palladium (0.829 g, 0.718 mmol), and toluene (150 mL). The water-methanol solution was added via cannula to the toluene solution, and the biphasic mixture was heated to 80° C. overnight. At this time 1H NMR spectroscopic analysis of an aliquot indicated that the reaction was complete. The clear yellow organic layer was separated, dried with brine, then over magnesium sulfate. The crude product was purified by chromatography on silica using 1:1 hexanes:dichloromethane elutant and increasing the strength by addition of up to 10% EtOAc. The product was isolated as a sticky oil (4.7 g, 840%). 1H NMR (CD2Cl2, 500 MHz): 10.0 (s, 1H), 7.83-7.92 (m, 2H), 7.56 (d, 1H), 7.50 (d, 1H), 7.44 (m, 1H), 7.36 (m, 2H), 7.17 (t, 2H), 7.01 (t, 1H), 7.0 (br d, 2H), 5.11 (s, 2H), 1.34 (s, 9H).

Workup

  1. customthe mixture was sparged with nitrogen for 30 min
  2. customIn a separate flask were combined, under nitrogen
  3. customThe clear yellow organic layer was separated
  4. dry with materialdried with brine
  5. customThe crude product was purified by chromatography on silica using 1:1 hexanes
  6. temperaturedichloromethane elutant and increasing the strength
  7. additionby addition of up to 10% EtOAc

Sources & evidence

ORD record
ord-f50792b32f6d43798993db0a2cc077e1
Source dataset
uspto-grants-2014_03
Patent number
US08674040B2

Reaction notes

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