PyBroP → 4-(2-((2s,3s)-2-Acetyl-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-oxoethyl)-2-chloro-3-methylbenzonitrile

HRID 132688Notes

Reaction equation

HRID 132688 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@@H:9]1[CH:21]([OH:23])[CH3:22])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[Cl:58][C:59]1[C:60]([CH3:71])=[C:61]([CH2:67]C(O)=O)[CH:62]=[CH:63][C:64]=1[C:65]#[N:66]>C(Cl)Cl.C1COCC1.CCOC(C)=O.C1(C)C=CC=CC=1>[C:21]([C@@H:9]1[C@@H:10]([O:13][Si:14]([C:17]([CH3:18])([CH3:19])[CH3:20])([CH3:15])[CH3:16])[CH2:11][CH2:12][N:8]1[C:6](=[O:7])[CH2:67][C:61]1[CH:62]=[CH:63][C:64]([C:65]#[N:66])=[C:59]([Cl:58])[C:60]=1[CH3:71])(=[O:23])[CH3:22]

Participants

9

Reactant 4

HCID 2733179PyBroPHCID 167319962-(3-Chloro-4-cyano-2-methylphenyl)acetic acidHCID 21863450Trifluoroacetic acid methylene chlorideHCID 66863428(2S,3S)-N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-(1-hydroxyethyl)pyrrolidine

Product 1

HCID 167318464-(2-((2s,3s)-2-Acetyl-3-(tert-butyldimethylsilyloxy)pyrrolidin-1-yl)-2-oxoethyl)-2-chloro-3-methylbenzonitrileYield 50.6%

Reagents, catalysts & solvents 4

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To compound 1L (480 mg, 1.4 mmol) was added 7 mL of 10% TFA/CH2Cl2 solution at RT, and stirred at 4 hr. A 7 mL toluene was added to the reaction mixture, and concentracted. It was dissolved in 5 mL of CH2Cl2, a solution of PyBrop (1.2 g, 2.5 mmol) and compound 1G (210 mg, 1 mmol) in 3 mL of THF were added followed by iPr2NET (520 μL, 3 mmol), and the stirring was continued for 3 hr at RT. It was concentracted, dissolved in EtOAc, washed with water, dried over Na2SO4, and concentrated. Purification by flash chromatography (silica gel, 30% EtOAc in hexanes) provided the title compound (220 mg). MS (ES) m/z 435 [M+H]+.

Workup

  1. waitthe stirring was continued for 3 hr at RT
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customPurification by flash chromatography (silica gel, 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-18d88f0a6bb648fb8cbf0a2d5c41ffd3
Source dataset
uspto-grants-2008_06
Patent number
US07388027B2

Reaction notes

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