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

HRID 254077Notes

Reaction equation

HRID 254077 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.Cl.C([O:40][C:41](=[O:45])[C@H:42]([CH3:44])[NH2:43])(C)(C)C.CN1CC[O:50][CH2:49][CH2:48]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.C1(C)C=CC=CC=1>[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][CH2:48][C:49]([NH:43][C@H:42]([C:41]([OH:40])=[O:45])[CH3:44])=[O:50])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11275390tert-Butyl alaninate hydrochlorideHCID 66842813[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid

Product 1

HCID 66842883N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}-L-alanineYield 101.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of [4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid (0.020 g, 0.041 mmol), L-Alanine tert-butyl ester hydrochloride (0.009 g, 0.050 mmol) and N-Methylmorpholine (0.018 ml, 0.163 mmol) in DCM (4 ml) was stirred for 5 min. TBTU (0.017 g, 0.053 mmol) was added. The formation of the ester was confirmed after 3 h. M/z: 611.1. TFA (3 ml) was added. After 2 h, the mixture was diluted with toluene (2 ml) and the solvent was removed under reduced pressure. The residue was purified by preparative HPLC, using a gradient of 20-50% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.023 g (>98%) of the title product was obtained as a white solid. M/z: 555.1. 1H NMR (DMSO, 400 MHz): δ 1.17 (d, 3H), 3.73-3.82 (m, 1H), 4.33 (d, 1H), 4.35 (ABq, 2H), 4.43 (s, 2H), 5.15 (d, 1H), 6.92-7.98 (m, 2H), 7.10-7.24 (m, 4H), 7.29-7.39 (m, 4H), 7.84 (d, 1H), 7.97-8.04 (m, 2H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. customThe residue was purified by preparative HPLC
  3. customAfter freeze-drying

Sources & evidence

ORD record
ord-3e18517d93844e75a8985cb5b0f2de89
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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