Hydrochloric Acid → Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetate

HRID 1176079Notes

Reaction equation

HRID 1176079 reaction equation
[Si:1]([O:8][C@H:9]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=2)[C@@H:13]1[C:24]1[CH:35]=[CH:34][C:27]([O:28][CH2:29][C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:25]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:43]([NH:46][S:47]([CH3:50])(=[O:49])=[O:48])[C:44]#[CH:45].C([O-])([O-])=O.[K+].[K+].Cl>O.CC#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.CCOC(C)=O>[Si:1]([O:8][C@H:9]([C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:10][S:11][C@H:12]1[C:15](=[O:16])[N:14]([C:17]2[CH:22]=[CH:21][C:20]([C:45]#[C:44][CH2:43][NH:46][S:47]([CH3:50])(=[O:49])=[O:48])=[CH:19][CH:18]=2)[C@@H:13]1[C:24]1[CH:35]=[CH:34][C:27]([O:28][CH2:29][C:30]([O:32][CH3:33])=[O:31])=[CH:26][CH:25]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 14025440N-(Prop-2-yn-1-yl)methanesulfonamideHCID 86628621Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-iodophenyl)-4-oxoazetidin-2-yl]phenoxy}acetate

Product 1

HCID 86628622Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-{3-[(methylsulfonyl)amino]prop-1-yn-1-yl}phenyl)-4-oxoazetidin-2-yl]phenoxy}acetate

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Methyl {4-[(2R,3R)-3-{[(2R)-2-{[tert-butyl(dimethyl)silyl]oxy}-2-(4-fluorophenyl)ethyl]thio}-1-(4-iodophenyl)-4-oxoazetidin-2-yl]phenoxy}acetate (500 mg, 0.69 mmol) and N-prop-2-yn-1-ylmethanesulfonamide (150 mg, 1.13 mmol) were mixed in 15 ml water and 4 ml MeCN. K2CO3 (220 mg, 1.59 mmol), Pd(PPh3)4 (40 mg, 5 mol %) and CuI (13 mg, 10 mol %) were added. The solution was stirred at 50° C. for 2 h and at ambient temperature over night. EtOAc (20 ml) and 2 M HCl (1 ml) were added. The mixture was stirred for 5 min and the phases were separated. The aqueous phase was extracted with EtOAc. The combined organic phases were washed with 2% NaHCO3, brine (2×), dried with MgSO4 and concentrated to yield the title compound. M/z: 725.3 (M−1). 1H-NMR (400 MHz, DMSO-d6) δ: −0.18 (s, 3H), −0.04 (s, 3H), 0.77 (s, 9H), 2.85-3.02 (m, 5H), 3.69 (s, 3H), 3.80 (dd, 1H), 4.01 (d, 2H), 4.29 (d, 1H), 4.79 (s, 2H), 4.91 (dd, 1H), 5.11 (d, 1H), 6.95 (d, 2H), 7.09-7.18 (m, 2H), 7.18-7.25 (d, 2H), 7.32-7.42 (m, 6H).

Workup

  1. stirringThe mixture was stirred for 5 min
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with EtOAc
  4. washThe combined organic phases were washed with 2% NaHCO3, brine (2×)
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f5046f567476442e8ba7fb35f473ead5
Source dataset
uspto-grants-2010_11
Patent number
US07842684B2

Reaction notes

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