Diisopropylethylamine → (2S,4R)-methyl 1-((S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate

HRID 1043413Notes

Reaction equation

HRID 1043413 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:25]([O:31][C:32]([NH:34][C@@H:35]([C:39]([CH3:42])([CH3:41])[CH3:40])[C:36]([OH:38])=O)=[O:33])[CH2:26][CH2:27][CH2:28][CH:29]=[CH2:30].CCN(C(C)C)C(C)C.[CH3:52][O:53][C@:54]1([C:63]2[CH:68]=[CH:67][C:66]([C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=3[CH:75]=[CH2:76])=[CH:65][CH:64]=2)[CH2:58][NH:57][C@H:56]([C:59]([O:61][CH3:62])=[O:60])[CH2:55]1>C(Cl)Cl>[CH2:25]([O:31][C:32]([NH:34][C@@H:35]([C:39]([CH3:42])([CH3:41])[CH3:40])[C:36]([N:57]1[CH2:58][C@:54]([O:53][CH3:52])([C:63]2[CH:64]=[CH:65][C:66]([C:69]3[CH:74]=[CH:73][CH:72]=[CH:71][C:70]=3[CH:75]=[CH2:76])=[CH:67][CH:68]=2)[CH2:55][C@H:56]1[C:59]([O:61][CH3:62])=[O:60])=[O:38])=[O:33])[CH2:26][CH2:27][CH2:28][CH:29]=[CH2:30]

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 45378514N-{[(Hex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valineHCID 59266525(2S,4R)-methyl 4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate

Product 1

HCID 59266504(2S,4R)-methyl 1-((S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2'-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HATU (139 mg, 0.365 mmol) was added to a solution of (S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoic acid (128 mg, 0.498 mmol), DIEA (0.174 mL, 0.996 mmol) and (2S,4R)-methyl 4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate (112 mg, 0.332 mmol) in DCM (5 mL). The reaction was stirred at r.t. overnight. The reaction was evaporated and purified on the Biotage (10-40% EtOAc in hexanes) to give (2S,4R)-methyl 1-((S)-2-((hex-5-enyloxy)carbonylamino)-3,3-dimethylbutanoyl)-4-methoxy-4-(2′-vinylbiphenyl-4-yl)pyrrolidine-2-carboxylate (151 mg, 79% yield) as a clear oil. LCMS: rt=2.05 min. [M+Na]30 =599; Phenomenex-Luna C-18 (5μ) (3.0×50 mm); Solvent A=10% acetonitrile—90% water—0.1% TFA, Solvent B=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 on the Biotage (10-40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-70fbe462c0d14d4aa1b1d43e3e88fe6b
Source dataset
uspto-grants-2013_10
Patent number
US08563505B2

Reaction notes

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