3-Iodobenzyl alcohol → HCID 59371365, compound

HRID 2095360Notes

Reaction equation

HRID 2095360 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:20]#[CH:21])[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].I[C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26][OH:27]>[Cu]I.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>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:19]=[C:18]([C:20]#[C:21][C:23]2[CH:24]=[C:25]([CH2:26][OH:27])[CH:28]=[CH:29][CH:30]=2)[CH:17]=[N:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 423003-Iodobenzyl alcoholHCID 56595566HCID 56595566, compound

Product 1

HCID 59371365HCID 59371365, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalyst

Procedure

A small resealable tube with stir bar was charged with 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-ethynylpyridine (168 mg, 583 μmol), copper(I) iodide (11 mg, 58 μmol, 0.1 equiv.), and bis(triphenylphosphine)palladium(II) chloride (43 mg, 58 μmol, 0.1 equiv.). To these reactants was added a solution of m-iodobenzyl alcohol (136 mg, 581 μmol, 1 equiv.). The mixture was purged with nitrogen through a needle, then the tube was capped, and the brown suspension was stirred at room temperature for 18.5 h. Solids were removed by suction filtration over celite and were washed with three portions of EtOAc (4 mL each). The solution was evaporated. TLC analysis (silica gel, EtOAc/hexane 3:1) showed, besides some PPh3 and baseline material, a single spot (Rf 0.3). The brown crude product was purified by CC on silica gel (24×2.5 cm, EtOAc/hexane 3:1 changing to 1:0 after appearance of the product). The product-containing fractions were evaporated and dried (50° C./oil pump) to yield 189 mg (82%) of a light-amber glass. 1H NMR (CDCl3, TMS, 250 MHz) δ 8.35 (d, 1H, J=1.4 Hz), 8.28 (d, 1H, J=2.7 Hz), 7.57 (narrow m, 1H), 7.49-7.43 (m, 1H), 7.43-7.32 (m, 3H), 4.73 (s, 2H), 4.53 (m, 1H), 4.35, 4.14 (ABq, 2H, J=10.1 Hz, low-field part br d, J=4.3 Hz, high-field part d, J=2.9 Hz), 3.90 (t, 2H, J=7.6 Hz), 2.47-2.21 (m, 3H, apparently including OH), 1.43 (s, 9H); 13C NMR (CDCl3, 62.5 MHz) δ 156.0, 154.4, 144.3, 141.8, 137.4, 130.3, 129.8, 128.3, 127.2, 123.0, 122.2, 120.5, 92.5, 85.4, 79.7, 68.5, 63.9, 59.8, 46.9 (br), 28.2, 18.8; MS (EI) m/z 394 (M+, 2.7%), 321 (3.8%), 294 (14%), 293 (11%), 265 (10%), 238 (22%), 100 (23%), 57 (100%), 56 (73%).

Workup

  1. customThe mixture was purged with nitrogen through a needle
  2. customthe tube was capped
  3. stirringthe brown suspension was stirred at room temperature for 18.5 h
  4. customSolids were removed by suction filtration over celite
  5. washwere washed with three portions of EtOAc (4 mL each)
  6. customThe solution was evaporated
  7. customThe brown crude product was purified by CC on silica gel (24×2.5 cm, EtOAc/hexane 3:1 changing to 1:0 after appearance of the product)
  8. customThe product-containing fractions were evaporated
  9. customdried (50° C./oil pump)
  10. customto yield 189 mg (82%) of a light-amber glass

Sources & evidence

ORD record
ord-9d47246740b84af99416748dbcd97a23
Source dataset
uspto-grants-2013_05
Patent number
US08445684B2

Reaction notes

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