Diisopropylethylamine → tert-Butyl [3-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)phenyl]carbamate

HRID 541747

Reaction equation

HRID 541747 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:6]=[CH:7][CH:8]=1)#[CH:2].I[C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31].C(N(CC)C(C)C)(C)C>C1COCC1.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>[C:30]([O:29][C:28]([NH:27][C:19]1[CH:20]=[CH:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:18]=1[C:2]#[C:1][C:3]1[CH:4]=[C:5]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[CH:6]=[CH:7][CH:8]=1)=[O:34])([CH3:33])([CH3:31])[CH3:32]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 7098713Tert-butyl 4-nitro-2-iodophenylcarbamateHCID 11275982tert-Butyl 3-ethynylphenylcarbamate

Product 1

HCID 57962078tert-Butyl [3-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)phenyl]carbamateYield 85%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

A solution of tert-butyl (3-ethynylphenyl)carbamate (12.7 g, 58.5 mmol), tert-butyl (2-iodo-4-nitrophenyl)carbamate (14.2 g, 39.0 mmol), bis(triphenylphosphine)palladium(II) chloride (1.37 g, 1.95 mmol), and copper(I) iodide (371 mg, 1.95 mmol) in THF (200 mL) was treated with N,N-diisopropylethylamine (7.47 mL, 42.9 mmol) dropwise and stirred at 20° C. overnight. The reaction mixture was concentrated and diluted with water (200 mL) and ethyl acetate (200 mL). The organic layer was separated, washed with brine, dried with sodium sulfate, filtered, and concentrated to give a yellow/brown solid which was washed with ethyl acetate to give the desired product as light yellow solid (15 g, 85%). LCMS calculated for C24H27N3O6Na (M+Na)+: m/z=476.2.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with water (200 mL) and ethyl acetate (200 mL)
  3. customThe organic layer was separated
  4. washwashed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a yellow/brown solid which
  9. washwas washed with ethyl acetate

Sources & evidence

ORD record
ord-885e2872087d49939c7838011470e71f
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Linked notes

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