methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate → tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate

HRID 1779177Notes

Reaction equation

HRID 1779177 reaction equation
[CH2:1]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]/[CH:15]=[CH:16]/[C@H:17]([C:31](N1[C@@H](C(C)C)C(C2C=CC=CC=2)(C2C=CC=CC=2)SC1=O)=[O:32])[C@@:18]([OH:30])([CH2:26][CH2:27][O:28][CH3:29])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[NH2:54][C@@H:55]([CH2:60][C:61]1[CH:66]=[CH:65][C:64]([O:67][CH2:68][C:69]#[C:70][CH3:71])=[CH:63][CH:62]=1)[C:56]([O:58][CH3:59])=[O:57]>ClCCl>[CH2:68]([O:67][C:64]1[CH:63]=[CH:62][C:61]([CH2:60][C@H:55]([NH:54][C:31]([C@@H:17](/[CH:16]=[CH:15]/[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][S:8][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])[C@@:18]([OH:30])([CH2:26][CH2:27][O:28][CH3:29])[C:19]([O:21][C:22]([CH3:24])([CH3:25])[CH3:23])=[O:20])=[O:32])[C:56]([O:58][CH3:59])=[O:57])=[CH:66][CH:65]=1)[C:69]#[C:70][CH3:71]

Participants

4

Reactant 2

HCID 58239373methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionateHCID 118260125tert-Butyl (E)-(2S,3S)-11-heptylsulfanyl-2-hydroxy-3-((S)-4-isopropyl-2-oxo-5,5-diphenyl-thiazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-undec-4-enoate

Product 1

HCID 118260126tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoateYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

tert-Butyl (E)-(2S,3S)-11-heptylsulfanyl-2-hydroxy-3-((S)-4-isopropyl-2-oxo-5,5-diphenyl-thiazolidine-3-carbonyl)-2-(2-methoxy-ethyl)-undec-4-enoate (No. 6804239; 68.3 mg, 0.0889 mmol) and methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate (33.0 mg, 0.133 mmol) were dissolved in dichloromethane. The solvent was distilled off under reduced pressure. The resulting mixture was stirred at 50° C. for 5 days, cooled to room temperature, and then extracted by adding ethyl acetate and water. The organic layer was washed with a saturated brine, dried over anhydrous sodium sulfate, and then filtered. The solvent was distilled out of the filtrate under reduced pressure. The residue was purified with SP1 (SiO2 cartridge, 25% ethyl acetate/n-hexane, Rf=0.1) to obtain tert-butyl (E)-(2S,3S)-3-[(S)-2-(4-but-2-ynyloxy-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-11-heptylsulfanyl-2-hydroxy-2-(2-methoxy-ethyl)-undec-4-enoate (No. 6804240; 50.9 mg, 80% yield)

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. temperaturecooled to room temperature
  3. extractionextracted
  4. additionby adding ethyl acetate and water
  5. washThe organic layer was washed with a saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. distillationThe solvent was distilled out of the filtrate under reduced pressure
  9. customThe residue was purified with SP1 (SiO2 cartridge, 25% ethyl acetate/n-hexane, Rf=0.1)

Sources & evidence

ORD record
ord-2d17d9baf93a4134bbdab810abac0f0b
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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