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

HRID 254112Notes

Reaction equation

HRID 254112 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](OC)=[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(O)=O)=[CH:27][CH:26]=2)=[CH:4][CH:3]=1.Cl.NC[C:39]([NH:41][C@@H:42]([C:46]([O:48]C(C)(C)C)=[O:47])C(C)C)=[O:40].CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)[F:78].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:18]=[CH:19][C:20]([F:78])=[CH:21][CH:22]=3)=[O:16])[C@H:9]2[C:25]2[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:39]([NH:41][CH2:42][C:46]([OH:48])=[O:47])=[O:40])=[CH:34][CH:35]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 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 acidHCID 86613090tert-butyl glycyl-D-valinate hydrochloride

Product 1

HCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycineYield 89.5%

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 (0.0153 g, 0.031 mmol), tert-butyl glycyl-D-valinate hydrochloride (0.0099 g, 0.037 mmol) and N-methylmorpholine (0.010 ml, 0.091 mmol) in DCM (2 ml) was stirred at room temperature. TBTU (0.016 g, 0.050 mmol) was added and the mixture was stirred for 3.5 h. Trifluoroacetic acid (0.5 ml) was added and after 3.5 h the solvent was removed under reduced pressure. The residue was purified by preparative HPLC on a Kromasil C8-column using a gradient of 5-100% MeCN in 0.15% trifluoroacetic acid buffer as eluent. The solvent was removed under reduced pressure and 0.015 g (74%) of the title product was obtained. M/z 652.20.

Workup

  1. stirringthe mixture was stirred for 3.5 h
  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-03adb862790142d9a2dca76e28d169ab
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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