Triethylamine → 4-methoxybenzyl [(R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)pent-4-yn-1-yl]carbamate

HRID 243657

Reaction equation

HRID 243657 reaction equation
[Si:1]([O:8][C@H:9]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C@H:10]([NH:15][C:16](=[O:27])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[CH2:11][CH2:12][C:13]#[CH:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].I[C:35]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=1.C(N(CC)CC)C>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I>[Si:1]([O:8][C@H:9]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C@H:10]([NH:15][C:16](=[O:27])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[CH2:11][CH2:12][C:13]#[C:14][C:35]1[CH:40]=[CH:39][C:38]([N+:41]([O-:43])=[O:42])=[CH:37][CH:36]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 124951-Iodo-4-nitrobenzeneHCID 579075124-Methoxybenzyl {(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pent-4-yn-1-yl}carbamate

Product 1

HCID 579075794-methoxybenzyl [(R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)pent-4-yn-1-yl]carbamate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of acetylene (from Step E, 40 g, 80 mmol) and 4-iodonitrobenzene (21.8 g, 88 mmol) in anhydrous DMF (500 ml) was added triethylamine (111 mL, 797 mmol). Pd(dppf)Cl2 (1.95 g, 2.39 mmol) and copper(I) iodide (910 mg, 4.78 mmol) was added and the mixture degassed with nitrogen (bubble 15 min) and the resulting solution stirred at room temperature for 5 h. The mixture was poured into water (1200 m) and extracted with EtOAc (3×300 mL). The combined organics were then washed with water (2×500 mL), sat. NaCl (200 mL), dried over magnesium sulfate, filtered and evaporated under vacuum. Residue was purified by MPLC (Horizon Biotage 2× Flash 65i) eluting with a gradient of 0-30% ethyl acetate in hexane to give 41 g (84%) as a dark red oil. %). 1H NMR (500 MHz, CDCl3): 8.11-8.04 (m, 2H), 7.94-8.01 (m, 1H), 7.38-7.21 (m, 8H), 6.87 (d, J=8.4 Hz, 2H), 4.98 (s, 2H), 4.77-4.59 (m, 2H), 4.00-3.95 (m, 3H), 3.81 (s, 3H), 2.56 (t, J=7.1 Hz, H=2H), 2.00-1.95 (m, 1H), 1.66-1.61 (m, 1H), 0.93 (s, 9H), 0.10 (s, 3H), −0.10 (s, 3H). LC-MS: m/z (ES) 589.3 (MH)+, 611.2 (MNa)+.

Workup

  1. customthe mixture degassed with nitrogen (bubble 15 min)
  2. additionThe mixture was poured into water (1200 m)
  3. extractionextracted with EtOAc (3×300 mL)
  4. washThe combined organics were then washed with water (2×500 mL), sat. NaCl (200 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customResidue was purified by MPLC (Horizon Biotage 2× Flash 65i)
  9. washeluting with a gradient of 0-30% ethyl acetate in hexane
  10. customto give 41 g (84%) as a dark red oil

Sources & evidence

ORD record
ord-36cc65d3835f40289c00a47adf7be022
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Linked notes

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