Methanol → N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-N,2-dimethylalanine

HRID 254053Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2C(=O)[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:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([OH:36])=O)=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:68][NH:69][C:70]([CH3:75])([CH3:74])[C:71]([OH:73])=[O:72].[BH4-].[Na+].[CH3:78][OH:79]>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:78](=[O:79])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[OH:16])[C@H:9]2[C:24]2[CH:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([N:69]([CH3:68])[C:70]([CH3:75])([C:71]([OH:73])=[O:72])[CH3:74])=[O:36])=[O:31])=[CH:26][CH:25]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 30 °C

Procedure

To mixture of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.020 g, 0.037 mmol) and NMM (0.012 ml, 0.109 mmol) in DMF (3 ml) at 30° C. was added TBTU (0.018 g, 0.056 mmol). The reaction mixture was stirred for 20 min after which 2-(methylamino)isobutyric acid (0.005 g, 0.038 mmol) was added. The mixture was stirred at 30° C. for 20 h before the reaction was quenched by the addition of water (1 ml). The mixture was diluted with MeOH (2 ml) and NaBH4(0.018 g, 0.486 mmol) was added. After 10 min the reaction was quenched by the addition of a 0.1M ammonium acetate buffer (2 ml) and most of the methanol was removed under reduced pressure. The remaining solution was purified by preparative HPLC using a gradient of 20-50% MeCN in a 0.1M ammonium acetate buffer as eluent. Freeze-drying of the pure fractions gave the desired product as a white solid (0.012 g, 50% yield).

Workup

additionwas added
customwas quenched by the addition of water (1 ml)
additionwas added
customAfter 10 min the reaction was quenched by the addition of a 0.1M ammonium acetate buffer (2 ml) and most of the methanol
customwas removed under reduced pressure
customThe remaining solution was purified by preparative HPLC
customFreeze-drying of the pure fractions

Sources & evidence

ORD record: ord-929f8eb9fead4e4dacd5c1e19da211dd
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07871998B2

Reaction notes

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