Diisopropylethylamine → (2S,4R)-methyl 1-((S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate

HRID 1043433Notes

Reaction equation

HRID 1043433 reaction equation
[CH2:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])[CH2:2][CH:3]=[CH2:4].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:50][O:51][C@:52]1([C:61]2[CH:62]=[C:63]([C:67]3[CH:72]=[CH:71][CH:70]=[C:69]([CH:73]=[CH2:74])[CH:68]=3)[CH:64]=[CH:65][CH:66]=2)[CH2:56][NH:55][C@H:54]([C:57]([O:59][CH3:60])=[O:58])[CH2:53]1>C(Cl)Cl>[CH2:1]([O:5][C:6]([NH:8][C@@H:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([N:55]1[CH2:56][C@:52]([O:51][CH3:50])([C:61]2[CH:62]=[C:63]([C:67]3[CH:72]=[CH:71][CH:70]=[C:69]([CH:73]=[CH2:74])[CH:68]=3)[CH:64]=[CH:65][CH:66]=2)[CH2:53][C@H:54]1[C:57]([O:59][CH3:60])=[O:58])=[O:12])=[O:7])[CH2:2][CH:3]=[CH2:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 45378513(S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoic acidHCID 59266492(2S,4R)-methyl 4-methoxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate

Product 1

HCID 59266577(2S,4R)-methyl 1-((S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(3'-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylateYield 68.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (255 mg, 1.111 mmol), DIEA (0.40 mL, 2.223 mmol) and HATU (310 mg, 0.815 mmol) were added to a solution of (2S,4R)-methyl 4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate (250 mg 0.741 mmol) in DCM (3 mL). The reaction was stirred at r.t. for 2 hrs. The reaction was evaporated and purified by flash chromatography on the Biotage (10-40% EtOAc:Hex) to give (2S,4R)-methyl 1-((S)-2-((but-3-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(3′-vinylbiphenyl-3-yl)pyrrolidine-2-carboxylate (277 mg, 0.505 mmol, 68% yield) as a white foam. LCMS: rt=2.31 min. [M+H]+=549; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent 13=90% acetonitrile—10% water—0.1% TFA; gradient 0% to 100% solvent B over 2 min. and then hold for 1 min.; 4 mL/min, inj. vol.=5 uL; wavelength=220.

Workup

  1. customThe reaction was evaporated
  2. custompurified by flash chromatography on the Biotage (10-40% EtOAc:Hex)

Sources & evidence

ORD record
ord-c898a078a6fd40e096d6574fa46ce9d2
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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