Triethylamine → HCID 69028940, compound

HRID 489594Notes

Reaction equation

HRID 489594 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:28][CH2:27][N:26]([C:29](=[O:38])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]#[CH:37])[CH:31]=3)[CH2:25][CH2:24]2)[CH:18]=1)[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].I[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(CC)CC)C>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.[Cu]I.CN(C)C=O>[C:12]([O:11][C:9]([N:8]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[CH2:28][CH2:27][N:26]([C:29](=[O:38])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([C:36]#[C:37][C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[CH:31]=3)[CH2:25][CH2:24]2)[CH:18]=1)[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:10])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 11575IodobenzeneHCID 22266181HCID 22266181, compound

Product 1

HCID 69028940HCID 69028940, compoundYield 84.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of N,N-bis-(tert-butoxycarbonyl)-3-[1-(3-ethynyl-benzoyl)-piperidin-4-yl]-benzylamine (0.24 g, 0.46 mmol), iodobenzene (95 mg, 0.46 mmol), dichlorobis(triphenylphosphine)palladium (II) (35 mg, 0.05 mmol), copper (I) iodide (26 mg, 0.14 mmol), triethylamine (0.57 ml, 4.1 mmol) and anhydrous dimethylformamide (8 ml) was stirred at ambient temperature under nitrogen for 18 hours. The solvent was removed under vacuum and the residue was partitioned between ethyl acetate (3 lots of 50 ml) and water (20 ml). The combined organic layers were washed with brine (50 ml), then dried over magnesium sulfate and then concentrated under vacuum. The residue was subjected to chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (3:2, v/v) to give N,N-bis-(tert-butoxycarbonyl)-3-[1-(3-phenylethynyl-benzoyl)-piperidin-4-yl]-benzylamine as a yellow oil (0.23 g). 1H NMR (CDCl3, 500 MHz): δ 7.58 (m, 4H), 7.40 (m, 5H), 7.25 (m, (m, 1H), 7.10 (m, 3H), 4.90 (br m, 1H), 4.79 (s, 2H), 3.80 (br m, 1H), 3.15 (br m, 1H), 2.84 (br, m, 1H), 2.78 (br m, 1H), 1.95 (m, 1H), 1.80 (m, 3H), 1.42 (s, 18H). MS(EI): 617(M++Na).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue was partitioned between ethyl acetate (3 lots of 50 ml) and water (20 ml)
  3. washThe combined organic layers were washed with brine (50 ml)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under vacuum
  6. additionThe residue was subjected to chromatography on silica gel eluting with a mixture of cyclohexane and ethyl acetate (3:2

Sources & evidence

ORD record
ord-657d1b75649347caaf11ac8d19117af7
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Reaction notes

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