Diisopropylethylamine → 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 1779184Notes

Reaction equation

HRID 1779184 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]([O-:33])=O)[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].Cl.[NH2:35][C@@H:36]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH2:49][C:50]#[C:51][CH3:52])=[CH:44][CH:43]=1)[C:37]([O:39][CH3:40])=[O:38].F[P-](F)(F)(F)(F)F.CN([C+](N(C)C)N1C2C(=NC=CC=2)[N+]([O-])=N1)C.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[CH2:49]([O:48][C:45]1[CH:46]=[CH:47][C:42]([CH2:41][C@H:36]([NH:35][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]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[O:33])[C:37]([O:39][CH3:40])=[O:38])=[CH:43][CH:44]=1)[C:50]#[C:51][CH3:52]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 67118240(S)-2-amino-3-{4-(2-butynyloxy)phenyl}-propionic acid methyl ester hydrochlorideHCID 1317348581-tert-butyl (2S,3S)-3-((E)-8-heptylsulfanyl-oct-1-enyl)-2-hydroxy-2-(2-methoxy-ethyl)-succinateHCID 178484292HCID 178484292, compound

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 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, at room temperature, to 1-tert-butyl (2S,3S)-3-((E)-8-heptylsulfanyl-oct-1-enyl)-2-hydroxy-2-(2-methoxy-ethyl)-succinate (210.0 mg, 0.430 mmol) obtained in Step C-6b in DMF (4.2 mL), were added methyl (S)-2-amino-3-(4-but-2-ynyloxy-phenyl)-propionate hydrochloride (148.4 mg, 0.516 mmol), 1-[bis(dimethylamino)methyliumyl]-1H-1,2,3-triazolo[4,5-B]pyridine-3-oxide hexafluorophosphate (179.1 mg, 0.473 mmol), and N,N-diisopropylethylamine (299.0 μL, 1.72 mmol) in order. After stirring for 8 hours, the progress of the reaction was stopped by adding water. The mixture was extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was then washed with water and a saturated brine, dried over anhydrous sodium sulfate, and then filtered. The solvent was distilled out of the filtrate under reduced pressure. The resulting residue was purified with SP1 (SiO2 cartridge, 20% ethyl acetate/n-hexane, Rf=0.35) 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; 249.3 mg, 2 steps, 80% yield).

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. washThe combined organic layer was then washed with water
  4. dry with materiala saturated brine, dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. distillationThe solvent was distilled out of the filtrate under reduced pressure
  7. customThe resulting residue was purified with SP1 (SiO2 cartridge, 20% ethyl acetate/n-hexane, Rf=0.35)

Sources & evidence

ORD record
ord-84a9d02dded745c1bc5946a911ad3461
Source dataset
uspto-grants-2016_02
Patent number
US09266853B2

Reaction notes

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