4-Methylmorpholine → N-{[4-((2R,3R)-1-(4-chlorophenyl)-3-{[2-(4-chlorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

HRID 250297Notes

Reaction equation

HRID 250297 reaction equation
[Cl: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]([Cl:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:34]=[CH:33][C:27]([O:28][CH2:29][C:30](O)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.Cl.[NH2:43][CH2:44][C:45]([O:47]C(C)(C)C)=[O:46].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl>[Cl: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]([Cl:23])=[CH:19][CH:18]=3)=[O:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:43][CH2:44][C:45]([OH:47])=[O:46])=[O:31])=[CH:33][CH:34]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2725036Glycine tert-butyl ester hydrochlorideHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 66842820[4-((2R,3R)-1-(4-Chlorophenyl)-3-{[2-(4-chlorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid

Product 1

HCID 66842755N-{[4-((2R,3R)-1-(4-chlorophenyl)-3-{[2-(4-chlorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of [4-((2R,3R)-1-(4-chlorophenyl)-3-{[2-(4-chlorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid, 302.1 mg, 0.585 mmol) in DCM (6 ml) were added N-methylmorpholine (190 μl, 1.728 mmol) and tert-butyl glycinate hydrochloride (133.4 mg, 0.80 mmol). After 10 minutes TBTU (224.3 mg, 0.67 mmol) was added and the reaction mixture was stirred at ambient temperature for 60 hours. The intermediate tert-butylester of the title compound was confirmed. M/z: 626.88 (M−H). DCM (10 ml) and water (15 ml) were added and the mixture was acidified to pH of 3 with KHSO4 (2M). The organic phase was washed with water (2×15 ml), the combined water phases were extracted with DCM (10 ml), dried over Na2SO4, filtered and the solvent was evaporated off. A solution of the residue (500 mg) in DCM (10 ml) and TFA (4 ml) was stirred at ambient temperature overnight. The solvent was removed under reduced presssure, toluene was used to assist the removal of TFA. The residue was purified with preparative HPLC on a C8 column. A gradient from 20 to 50% MeCN in 0.1M ammonium acetate buffer was used as eluent. After lyophilisation, the title compound was obtained as a white solid (166.9 mg, 50%). 1H-NMR (400 MHz, DMS-d6): 3.51 (d, 2H), 4.33 (d, 1H), 4.34 (s, 1H), 4.36 (s, 1H), 4.47 (s, 2H), 5.17 (d, 1H), 6.96 (d, 2H), 7.16-7.21 (m, 2H), 7.35 (d, 4H), 7.54-7.59 (m, 2H), 7.83-7.90 (brs, 1H), 7.91-7.95 (m, 2H). M/z: 571.04 (M−H) and 572.88 (M+H).

Sources & evidence

ORD record
ord-7c0687dda2a44881b8db43ef78a69b0d
Source dataset
uspto-grants-2011_01
Patent number
US07863265B2

Reaction notes

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