Triethylamine → (3R,4S)-1-[4-(3-aminoprop-1-yn-1-yl)phenyl]-4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one

HRID 1437823Notes

Reaction equation

HRID 1437823 reaction equation
[Si:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@H:15]2[N:18]([C:19]3[CH:24]=[CH:23][C:22](I)=[CH:21][CH:20]=3)[C:17](=[O:26])[C@@H:16]2[CH2:27][CH2:28][C@@H:29]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)[OH:30])=[CH:11][CH:10]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:38]([NH2:41])[C:39]#[CH:40].C(N(CC)CC)C>CN(C=O)C.[Cu]I>[NH2:41][CH2:38][C:39]#[C:40][C:22]1[CH:23]=[CH:24][C:19]([N:18]2[C@H:15]([C:12]3[CH:13]=[CH:14][C:9]([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[CH:10][CH:11]=3)[C@@H:16]([CH2:27][CH2:28][C@@H:29]([C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=3)[OH:30])[C:17]2=[O:26])=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 239041PropargylamineHCID 68977003(3R,4S)-4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-1-(4-iodophenyl)azetidin-2-one

Product 1

HCID 68976050(3R,4S)-1-[4-(3-aminoprop-1-yn-1-yl)phenyl]-4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 8 mg (0.013 mmol, 1 equiv.) (3R,4S)-4-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-1-(4-iodophenyl)azetidin-2-one (intermediate step A) in 0.5 mL DMF was added 2.2 mg (0.002 mmol, 0.15 equiv.) tetrakistriphenylphosphine palladium(0) and 0.8 mg (0.004 mmol, 0.3 equiv) copper(I) iodide. The solution was deoxygenated by a slow stream of anhydrous nitrogen delivered by a needle through a rubber septum. To the resulting solution was added by syringe 0.012 mL (0.177 mmol, 14 equiv.) propargyl amine and 0.012 mL (0.09 mmol, 7 equiv.) triethylamine. The resulting solution was stirred at room temperature for 1.25 hr at which time the solvent was removed under vacuum. The residue was purified by prep. Tlc eluting with CH2Cl2/MeOH (9/1) to afford the title compound. m/z (ES) 559.3 (MH+), 542.3 (MH−NH3+).

Workup

  1. customThe solution was deoxygenated by a slow stream of anhydrous nitrogen
  2. customwas removed under vacuum
  3. customThe residue was purified by prep

Sources & evidence

ORD record
ord-6ffc8fc9f27e43df965de51daa7498aa
Source dataset
uspto-grants-2009_11
Patent number
US07622449B2

Reaction notes

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