N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-valine → N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-hydroxy-2-(4-methoxyphenyl)ethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-valine

HRID 254022Notes

Reaction equation

HRID 254022 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:46]=[CH:45][C:28]([O:29][CH2:30][C:31]([NH:33][CH2:34][C:35]([NH:37][C@@H:38]([C:42]([OH:44])=[O:43])[CH:39]([CH3:41])[CH3:40])=[O:36])=[O:32])=[CH:27][CH:26]=2)=[CH:4][CH:3]=1>CO.C(O)(=O)C>[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][CH:15]([OH:16])[C:17]3[CH:18]=[CH:19][C:20]([O:23][CH3:24])=[CH:21][CH:22]=3)[C@H:9]2[C:25]2[CH:26]=[CH:27][C:28]([O:29][CH2:30][C:31]([NH:33][CH2:34][C:35]([NH:37][C@@H:38]([C:42]([OH:44])=[O:43])[CH:39]([CH3:41])[CH3:40])=[O:36])=[O:32])=[CH:45][CH:46]=2)=[CH:4][CH:3]=1

Participants

4

Reactant 1

HCID 66842834N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-valine

Product 1

HCID 66842768N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-hydroxy-2-(4-methoxyphenyl)ethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-valineYield 93.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-methoxyphenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl-D-valine (0.015 g, 0.023 mmol) was dissolved in methanol (3 ml). NABH4 (0.006 g, 0.158 mmol) was added and when the reaction was complete a few drops of acetic acid were added. The solvent was removed under reduced pressure and the residue was purified by preparative HPLC on a Kromasil C8-column using 25% MeCN in 0.1M ammonium acetate buffer as eluent. After freeze-drying, 0.014 g (93%) of the title product was obtained. NMR (500 MHz, CD3COOD) 0.93 (d, 3H), 0.95 (d, 3H), 2.12-2.22 (m, 1H), 2.91-3.07 (m, 2H), 3.75 (s, 1.5H), 3.76 (s, 1.5H), 3.94-4.06 (m, 3H), 4.33 (d, 1H), 4.60 (s, 2H), 4.72-4.78 (m, 1H), 4.81-4.88 (m, 1H), 6.79-6.83 (m, 2H), 6.97-7.08 (m, 4H), 7.20-7.36 (m, 6H).

Workup

  1. additionNABH4 (0.006 g, 0.158 mmol) was added
  2. additionwere added
  3. customThe solvent was removed under reduced pressure
  4. customthe residue was purified by preparative HPLC on a Kromasil C8-column
  5. customAfter freeze-drying

Sources & evidence

ORD record
ord-a0c0de69048a47529e4b643a0a450a66
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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