Acetic Acid → 4-methoxybenzyl [(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)-4-oxopentyl]carbamate

HRID 243658Notes

Reaction equation

HRID 243658 reaction equation
[Si:1]([O:8][C@H:9]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[C@H:10]([NH:24][C:25](=[O:36])[O:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)[CH2:11][CH2:12][C:13]#[C:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].N1CCCC1.C(O)(=[O:50])C>CN(C=O)C.O>[Si:1]([O:8][C@H:9]([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)[C@H:10]([NH:24][C:25](=[O:36])[O:26][CH2:27][C:28]1[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=1)[CH2:11][CH2:12][C:13](=[O:50])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 31268PyrrolidineHCID 579075794-methoxybenzyl [(R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)pent-4-yn-1-yl]carbamate

Product 1

HCID 579074284-methoxybenzyl [(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]-5-(4-nitrophenyl)-4-oxopentyl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of nitrophenyl acetylene (from Step F, 41 g, 65.5 mmol) in DMF (40 ml) was added pyrrolidine (14 mL, 196.5 mmol) and the resulting mixture heated at 80° C. for 3 h. The mixture was cooled to room temperature and a 10% solution of acetic acid in water (110 ml) was added, and the resulting solution stirred at room temperature for another 3 h. The mixture was poured into water (300 ml) and extracted with EtOAc (3×250 ml); combined EtOAc layers were washed with water (2×250 ml), sat. NaCl (100 ml), dried over MgSO4, filtered and evaporated. The residue was purified by Horizon Flash 75 eluting with a gradient rising from 100% Hexanes to 50% EtOAc in Hexanes to give 34 g (81%) as a dark orange oil. 1H NMR (500 MHz, CDCl3): 8.17-8.14 (m, 2H), 7.32-7.23 (m, 9H), 6.87 (d, J=8.4 Hz, 2H), 4.96 (d, J=12.2 Hz, 1H), 4.90 (d, J=12.1 Hz, 1H), 4.72 (d, J=3 Hz, 1H), 4.16-4.13 (m, 1H), 3.81 (s, 3H), 3.71-3.77 (m, 2H), 2.65-2.52 (m, 2H), 1.97-1.92 (m, 1H), 1.72-1.60 (m, 1H), 0.93 (s, 9H), 0.05 (s, 3H), −0.13 (s, 3H).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionextracted with EtOAc (3×250 ml)
  3. washcombined EtOAc layers were washed with water (2×250 ml), sat. NaCl (100 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by Horizon Flash 75 eluting with a gradient
  8. customto give 34 g (81%) as a dark orange oil

Sources & evidence

ORD record
ord-ccb11abe5a7545529ab0faa258da3db1
Source dataset
uspto-grants-2014_02
Patent number
US08653260B2

Reaction notes

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