1-Aminocyclopropane-1-carboxylic acid → 1-[(n-{[4-((2r,3r)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino]cyclopropanecarboxylic acid

HRID 254043

Reaction equation

HRID 254043 reaction equation
CN1CCOCC1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:30][C:31]1[CH:36]=[CH:35][C:34]([N:37]2[C:40](=[O:41])[C@H:39]([S:42][CH2:43][C:44]([C:46]3[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=3)=[O:45])[C@H:38]2[C:53]2[CH:67]=[CH:66][C:56]([O:57][CH2:58][C:59]([NH:61][CH2:62][C:63](O)=[O:64])=[O:60])=[CH:55][CH:54]=2)=[CH:33][CH:32]=1.[NH2:68][C:69]1([C:72]([OH:74])=[O:73])[CH2:71][CH2:70]1.[BH4-].[Na+]>CN(C=O)C.CO>[F:30][C:31]1[CH:32]=[CH:33][C:34]([N:37]2[C:40](=[O:41])[C@H:39]([S:42][CH2:43][CH:44]([C:46]3[CH:47]=[CH:48][C:49]([F:52])=[CH:50][CH:51]=3)[OH:45])[C@H:38]2[C:53]2[CH:54]=[CH:55][C:56]([O:57][CH2:58][C:59]([NH:61][CH2:62][C:63]([NH:68][C:69]3([C:72]([OH:74])=[O:73])[CH2:71][CH2:70]3)=[O:64])=[O:60])=[CH:66][CH:67]=2)=[CH:35][CH:36]=1

Participants

8

Reactant 5

HCID 5351-Aminocyclopropane-1-carboxylic acidHCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4311764Sodium borohydrideHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Product 1

HCID 668427281-[(n-{[4-((2r,3r)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-hydroxyethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycyl)amino]cyclopropanecarboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

N-Methyl morpholine (0.037 g, 0.370 mmol) and TBTU (0.039 g, 0.120 mmol) were added to a solution of N-{[4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine (0.025 g, 0.046 mmol) in DMF (2 ml) at 30° C. After 1 h, 1-aminocyclopropane carboxylic acid (0.019 g, 0.185 mmol) was added. After 1 h, the reaction was quenched by the addition of water (1 ml). After 10 minutes, MeOH (2 ml) and NaBH4 (0.035 g, 0.925 mmol) were added. Full conversion to the corresponding alcohol was obtained after 5 minutes. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml). The product was purified by preparative HPLC (eluent 0-50% CH3CN in 0.1M NH4OAc buffer). Freeze-drying of the pure fractions afforded the title compound (0.045 g, 78%) as a colourless solid. 1H NMR [(CD3)2SO), 400 MH] δ 0.78-0.88 (m, 2H), 1.08-1.22 (m, 2H), 2.84-2.94 (m, 2H), 3.63-3.72 (m, 2H), 4.24-4.29 (m, 1H), 4.48-4.52 (m, 2H), 4.68-4.75 (m, 1H), 5.03-5.06 (m, 1H), 6.96-7.37 (m, 12H), 7.78-8.36 (m, 2H).

Workup

  1. waitAfter 1 h
  2. customthe reaction was quenched by the addition of water (1 ml)
  3. waitAfter 10 minutes

Sources & evidence

ORD record
ord-837dc02baca54b1c83cf8df7d789dbce
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Linked notes

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