2-Methyl-3-butyn-2-ol → (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

HRID 661054Notes

Reaction equation

HRID 661054 reaction equation
Br[C:2]1[N:3]=[C:4]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][CH:6]=1.[CH3:36][C:37]([OH:41])([C:39]#[CH:40])[CH3:38]>CCN(CC)CC.Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[OH:41][C:37]([CH3:38])([CH3:36])[C:39]#[C:40][C:2]1[N:3]=[C:4]([N:7]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:8][C@@H:9]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[S:5][CH:6]=1

Participants

6

Reactant 2

HCID 82582-Methyl-3-butyn-2-olHCID 57633952(S)-tert-butyl 1-(N-(4-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate

Product 1

HCID 57634169(S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamateYield 91.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418903HCID 178418903, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

(S)-tert-butyl 1-(N-(4-bromothiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.25 g, 0.43 mmol) was taken up in 4 mL of Et3N. 2-Methylbut-3-yn-2-ol (0.21 mL, 2.2 mmol), dichlorobis(triphenylphosphino)-palladium(II) (0.030 g, 0.043 mmol), and copper(I) iodide (0.025 g, 0.13 mmol) were added. The mixture was stirred for 20 minutes. No reaction was observed, and the mixture was heated to 60° C. for 1 hour. The reaction was judged to be complete by LC/MS, the solvent was removed under reduced pressure, and the residue was purified by flash chromatography on silica gel (5% to 30% EtOAc/hexanes), to provide (S)-tert-butyl 1-(N-(4-(3-hydroxy-3-methylbut-1-ynyl)thiazol-2-yl)-tert-butoxylcarbonylamino)-3-(4-(trifluoromethyl)phenyl)propan-2-ylcarbamate (0.23 g, 91% yield): LCMS (M+H) 584 calc. for C28H37F3N3O5S 583.6.

Workup

  1. customthe solvent was removed under reduced pressure
  2. customthe residue was purified by flash chromatography on silica gel (5% to 30% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f215fbcab97b4367ac47c33959d1ca8f
Source dataset
uspto-grants-2011_12
Patent number
US08084479B2

Reaction notes

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