Water → HCID 53861764, compound

HRID 716075Notes

Reaction equation

HRID 716075 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](Br)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH:25]=2)O1.O.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:24]2[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH:25]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 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 89.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
90 °C

Procedure

A solution of commercial 1-(benzyloxy)-4-bromobenzene (104 g, 395 mmol) and commercial tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (147 g, 474 mmol) in 1100 mL of acetonitrile was purged with nitrogen for 2 min. Water (1100 mL) was added, followed by sodium carbonate (126 g, 1186 mmol) and tetrakis(triphenylphosphine)palladium (27.4 g, 23.7 mmol). The reaction mixture was purged with nitrogen for 5 min, and then heated to 90° C. and stirred for 16 h. The reaction mixture was then allowed to cool to rt and diluted with 1 L of ethyl acetate. The layers were separated, and the aqueous layer was extracted with two additional 250 mL portions of ethyl acetate. The organic layers were combined, washed with 200 mL of brine, dried over sodium sulfate, and evaporated in vacuo to provide an off-white solid. The product was purified by silica gel chromatography eluting with 6% ethyl acetate in petroleum ether to provide 129 g (88%) of the desired product. LC/MS RT (conditions A)=2.732 min, (M−H)+=364.0. 1H NMR (300 MHz, chloroform-d) δ 7.49-7.30 (m, 5H), 7.27 (d, J=10.7 Hz, 2H), 6.99-6.87 (m, 2H), 6.03-5.87 (m, 1H), 5.07 (s, 2H), 4.05 (d, J=2.6 Hz, 2H), 3.62 (t, J=5.7 Hz, 2H), 2.49 (br. s., 2H), 1.49 (s, 9H).

Workup

  1. customThe reaction mixture was purged with nitrogen for 5 min
  2. temperatureto cool to rt
  3. additiondiluted with 1 L of ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with two additional 250 mL portions of ethyl acetate
  6. washwashed with 200 mL of brine
  7. dry with materialdried over sodium sulfate
  8. customevaporated in vacuo
  9. customto provide an off-white solid
  10. customThe product was purified by silica gel chromatography
  11. washeluting with 6% ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-e1020ee820f04c35b59c9634cd742824
Source dataset
uspto-grants-2015_11
Patent number
US09187506B2

Reaction notes

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