1,2-Dimethoxyethane → HCID 53861764, compound

HRID 1507235Notes

Reaction equation

HRID 1507235 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]=2)O1.C(COC)OC.[CH2:29]([O:36][C:37]1[CH:42]=[CH:41][C:40](Br)=[CH:39][CH:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C(=O)([O-])[O-].[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH2:29]([O:36][C:37]1[CH:42]=[CH:41][C:40]([C:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:11][CH:10]=2)=[CH:39][CH:38]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 53861764HCID 53861764, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a stirring mixture of tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (16.45 g, 53 mmol), dimethoxyethane (200 mL) and water (50 mL) was added 1-(benzyloxy)-4-bromobenzene (14 g, 53 mmol), sodium carbonate (16.9 g, 160 mmol) and bis-(triphenylphosphine)palladium(II) chloride (1.867 g, 2.66 mmol) at rt. The reaction mixture was purged with nitrogen for 15 min, then heated at 80° C. for 4 h. The mixture was allowed to cool to rt and then was filtered through Celite and diluted with 200 mL of water. The mixture was then extracted three times with 200 mL of ethyl acetate and the combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The residue was subjected to silica gel chromatography eluting with 20% ethyl acetate/petroleum ether to obtain 16 g of tert-butyl 4-(4-(benzyloxy)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate (16 g, 82% yield) as an off-white solid. LCMS (method O) RT 1.32 min, m/z 366 (M+H+); 1H NMR (300 MHz, DMSO-d6) δ 1.47 (s, 9H), 2.42 (d, J=1.50 Hz, 2H), 3.52 (t, J=11.40 Hz, 2H), 3.97 (s, 2H), 5.11 (s, 2H), 6.04 (s, 1H), 6.98 (d, J=9.00 Hz, 2H), 7.30-7.46 (m, 7H).

Workup

  1. customThe reaction mixture was purged with nitrogen for 15 min
  2. temperatureto cool to rt
  3. filtrationwas filtered through Celite
  4. additiondiluted with 200 mL of water
  5. extractionThe mixture was then extracted three times with 200 mL of ethyl acetate
  6. dry with materialthe combined organic layers were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washeluting with 20% ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-63a5221d8e5d467497bc91218d15cc48
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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