Benzyl Alcohol → HCID 68008361, compound

HRID 533164Notes

Reaction equation

HRID 533164 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[CH2:6][CH2:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:9](=[O:12])[C:10]=2[CH:11]=1.[CH2:22]([OH:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.[Cu]I>[CH2:22]([O:29][C:2]1[CH:3]=[N:4][C:5]2[CH2:6][CH2:7][N:8]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[C:9](=[O:12])[C:10]=2[CH:11]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 13181,10-PhenanthrolineHCID 10796Cesium carbonateHCID 68008548HCID 68008548, compound

Product 1

HCID 68008361HCID 68008361, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

3-Bromo-6-(4-methoxybenzyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one (1.2 g, 3.5 mmol), benzyl alcohol (3.62 mL, 35.0 mmol), CuI (67.0 mg, 0.35 mmol), 1,10-phenanthroline (127.0 mg, 0.7 mmol) were mixed with Cs2CO3 (1.69 g, 5.2 mmol) in toluene (15.0 mL). The reaction was degassed, sealed in a microwave tube, heated to 110° C. for 1.5 day. The reaction mixture was passed through a Celite pad, diluted with H2O (50.0 mL), extracted with EtOAc (40.0×3 mL). The organic layers were combined, dried over MgSO4, concentrated in vacuo and purified by automated silica gel column chromatography (EtOAc/hexanes 0-60%). The compound was obtained as a sticky oil (1.08 g, 83%). 1HNMR (400 MHz, CDCl3) δ 8.39 (br s, 1H), 8.01 (d, J=3.2 Hz, 1H), 7.48-7.37 (overlapped, 5H), 7.30-7.27 (overlapped, 2H), 6.90 (d, J=8.8 Hz, 2H), 5.17 (s, 2H), 4.74 (s, 2H), 3.82 (s, 3H), 3.55 (t, J=6.8 Hz, 2H), 3.08 (t, J=6.8 Hz, 2H); LC-MS (M+H)=375.1.

Workup

  1. customThe reaction was degassed
  2. customsealed in a microwave tube
  3. additiondiluted with H2O (50.0 mL)
  4. extractionextracted with EtOAc (40.0×3 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by automated silica gel column chromatography (EtOAc/hexanes 0-60%)

Sources & evidence

ORD record
ord-8734c0a225b2477085b57864320dd2d9
Source dataset
uspto-grants-2014_10
Patent number
US08853237B2

Reaction notes

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