Diisopropylethylamine → tert-butyl (1S)-1-{[[(1S,2E)-3-cyano-1-isopropyl-2-propenyl](methyl)amino]carbonyl}-2,2-dimethylpropylcarbamate

HRID 133823Notes

Reaction equation

HRID 133823 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([C:13]([CH3:16])([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.[N:24]1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)[C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2N=N1.C[CH2:51][N:52](C(C)C)C(C)C.[CH3:59]CCCCC.CCOCC>ClCCl.FC(F)(F)C(O)=O.CC(C)[C@H](NC)/C=C/C#N>[C:28](/[CH:29]=[CH:30]/[C@@H:31]([N:52]([CH3:51])[C:10]([C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:12])[CH:32]([CH3:27])[CH3:59])#[N:24]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 50468592-{[(Tert-butoxy)carbonyl]amino}-3,3-dimethylbutanoic acidHCID 21584099Diethylether hexane

Product 1

HCID 86596607tert-butyl (1S)-1-{[[(1S,2E)-3-cyano-1-isopropyl-2-propenyl](methyl)amino]carbonyl}-2,2-dimethylpropylcarbamate

Reagents, catalysts & solvents 2

HCID 86596608(E,4S)-5-methyl-4-(methylamino)-2-hexenenitrile trifluoroacetic acidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of (E,4S)-5-methyl-4-(methylamino)-2-hexenenitrile trifluoroacetic acid (−1.68 mmol, from Reference Example 14), 2-tert-Butoxycarbonylamino-3,3-dimethyl-butyric acid (389 mg, 1.68 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP, 916 mg, 1.76 mmol) in dichloromethane (5 mL) at OC is added Hunig's base (0.877 mL, 5.04 mmol). After 5 min the cooling bath is removed. After 24 h 5% aqueous citric acid is added. The aqueous phase is washed with dichloromethane three times. The combined organic extracts are dried over anhydrous magnesium sulfate and concentrated in vacuo to give an oil. Chromatography (silica gel, hexane/ether) gave the title compound as a yellow foam (200 mg). MS (ES): m/z 352.0 (M+H)

Workup

  1. customAfter 5 min the cooling bath is removed
  2. additionAfter 24 h 5% aqueous citric acid is added
  3. washThe aqueous phase is washed with dichloromethane three times
  4. dry with materialThe combined organic extracts are dried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give an oil

Sources & evidence

ORD record
ord-442d842f365446f59ffd4f700dcc6777
Source dataset
uspto-grants-2008_06
Patent number
US07390910B2

Reaction notes

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