6-Bromopyridine-2-carbaldehyde → tert-Butyl {[1-(6-formylpyridin-2-yl)-2-naphthyl]methyl}phenylcarbamate

HRID 1944808Notes

Reaction equation

HRID 1944808 reaction equation
Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[C:10]1([N:16]([CH2:24][C:25]2[CH:34]=[CH:33][C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2B2OC(C)(C)C(C)(C)O2)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>CO.O.C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:8]([C:6]1[N:7]=[C:2]([C:26]2[C:27]3[C:32](=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:33]=[CH:34][C:25]=2[CH2:24][N:16]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:20])[CH3:21])[CH:3]=[CH:4][CH:5]=1)=[O:9]

Participants

7

Reactant 2

HCID 27570096-Bromopyridine-2-carbaldehydeHCID 66796055tert-Butyl phenyl{[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}carbamate

Product 1

HCID 86660102tert-Butyl {[1-(6-formylpyridin-2-yl)-2-naphthyl]methyl}phenylcarbamate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A solution of 24.3 g (84.8 mmol) of Na2CO3(H2O)1 in a mixture of 120 ml of methanol and 450 ml of water was added to a mixture of 6.30 g (33.9 mmol) of 6-bromopyridine-2-carbaldehyde, 15.6 g (33.9 mmol) of tert-butyl phenyl{[1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-naphthyl]methyl}carbamate and 1.96 g (1.70 mmol) of Pd(PPh3)4 in 600 ml of toluene by vigorous stirring at room temperature. The resulting mixture was stirred at 80° C. for 12 h. Further on, this mixture was cooled to room temperature, the organic layer was separated, dried over MgSO4, and then evaporated to dryness. The product was isolated by flash chromatography on silica gel 60 (40-63 um; eluent: hexanes-ethyl acetate=50:1 and then 10:1, vol.). Yield 9.50 g (64%). Anal. calc. for C28H26N2O3: C, 76.69; H, 5.98; N, 6.39. Found: C, 76.87; H, 6.12; N, 6.25. 1H NMR (CDCl3): 10.03 (s, 1H, CHO), 7.94-7.98 (m, 2H, 3,5-H in Py), 7.88 (m, 1H, 8-H in naphthyl), 7.83 (m, 1H, 4-H in Py), 7.75 (d, J=8.6 Hz, 1H, 4-H in naphthyl), 7.45 (m, 1H, 7-H in naphthyl), 7.34 (m, 1H, 6-H in naphthyl), 7.11-7.18 (m, 4H, 5-H in naphthyl and 3,4,5-H in Ph), 7.03 (d, J=8.6 Hz, 1H, 3-H in naphthyl), 6.93 (m, 2H, 2,6-H in Ph), 5.06 (d, J=15.9 Hz, 1H, CHH′N), 4.52 (d, J=15.9 Hz, 1H, CHH′N), 1.40 (s, 9H, tBu).

Workup

  1. stirringThe resulting mixture was stirred at 80° C. for 12 h
  2. temperatureFurther on, this mixture was cooled to room temperature
  3. customthe organic layer was separated
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe product was isolated by flash chromatography on silica gel 60 (40-63 um

Sources & evidence

ORD record
ord-cb88094aadf043bca5973faadca0e710
Source dataset
uspto-grants-2013_03
Patent number
US08394902B2

Reaction notes

Loading…