Trifluoroacetic acid → N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-D-alanine

HRID 254067Notes

Reaction equation

HRID 254067 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:34]=[CH:33][C:27]([O:28]CC(O)=O)=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.[NH2:35][C@@H:36]([C:38]([O:40]C(C)(C)C)=[O:39])[CH3:37].CN1CC[O:49][CH2:48][CH2:47]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:34]=[CH:33][C:27]([O:28][CH2:47][C:48]([NH:35][C@@H:36]([C:38]([OH:40])=[O:39])[CH3:37])=[O:49])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7359212tert-butyl (2R)-2-aminopropanoateHCID 66842813[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid

Product 1

HCID 66843258N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-D-alanineYield 99.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid (50 mg, 0.1 mmol), tert-butyl D-alaninate (23 mg, 0.12 mmol) and 4-methylmorpholine (31 mg, 0.31 mmol) were dissolved in DCM (1.5 ml) and stirred at room temperature for 5 minutes. TBTU (40 mg, 0.12 mmol) was added and the reaction mixture was stirred for 2 h. TFA (0.7 ml) was added and the solution was stirred for 90 minutes. TFA and DCM were removed under reduced pressure and the residue was dissolved in DCM and washed with water. The organic layer was dried over sodium sulphate and the solvent was removed under reduced pressure giving 55 mg (95%) of the title product. M/z: 553.0 (M−1).

Workup

  1. stirringthe reaction mixture was stirred for 2 h
  2. stirringthe solution was stirred for 90 minutes
  3. customTFA and DCM were removed under reduced pressure
  4. dissolutionthe residue was dissolved in DCM
  5. washwashed with water
  6. dry with materialThe organic layer was dried over sodium sulphate
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-6a2a9ad763c94ae5a62140d92fa2aa39
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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