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

HRID 254075Notes

Reaction equation

HRID 254075 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]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:25]2[CH:35]=[CH:34][C:28]([O:29][CH2:30][C:31]([OH:33])=O)=[CH:27][CH:26]=2)=[CH:4][CH:3]=1.Cl.[NH2:37][CH2:38][C:39]([O:41]C(C)(C)C)=[O:40].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.FC(F)(F)C(O)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][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]([O:23][CH3:24])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:25]2[CH:35]=[CH:34][C:28]([O:29][CH2:30][C:31]([NH:37][CH2:38][C:39]([OH:41])=[O:40])=[O:33])=[CH:27][CH:26]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842884[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid

Product 1

HCID 66842806N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycineYield 95.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of [4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid (0.150 g, 0.30 mmol), tert-butyl glycinate hydrochloride (0.0635 g, 0.38 mmol) and N-methylmorpholine (0.10 ml, 0.91 mmol) in DCM (2 ml) was stirred at room temperature. TBTU (0.128 g, 0.40 mmol) was added and the mixture was stirred overnight. Trifluoroacetic acid (4.0 ml) was added and after 2 h the solvent was removed under reduced pressure. The residue was purified by preparative HPLC on a Kromasil C8-column using 35% MeCN in 0.1M ammonium acetate buffer as eluent. The solvent was removed under reduced pressure and 0.159 g (95%) of the title product was obtained. M/z 553.02.

Workup

  1. stirringthe mixture was stirred overnight
  2. customwas removed under reduced pressure
  3. customThe residue was purified by preparative HPLC on a Kromasil C8-column
  4. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-eca67791f3344e0285b5f81e7feb2168
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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