4-Methylmorpholine → HCID 66842904, compound

HRID 254060Notes

Reaction equation

HRID 254060 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:38]=[CH:37][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34](O)=[O:35])=[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.[CH:68]1([CH2:73][C@H:74]([C:76]([OH:78])=[O:77])[NH2:75])[CH2:72][CH2:71][CH2:70][CH2:69]1.[BH4-].[Na+]>CN(C=O)C.CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:11](=[O:12])[C@H:10]([S:13][CH2:14][CH:15]([C:17]3[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=3)[OH:16])[C@H:9]2[C:24]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH:32][CH2:33][C:34]([NH:75][C@@H:74]([C:76]([OH:78])=[O:77])[CH2:73][CH:68]3[CH2:69][CH2:70][CH2:71][CH2:72]3)=[O:35])=[O:31])=[CH:37][CH:38]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4311764Sodium borohydrideHCID 6993046(R)-2-amino-3-cyclopentylpropanoic acidHCID 66842760N-{[4-((2R,3R)-1-(4-Fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio)-4-oxoazetidin-2-yl)phenoxy]acetyl}glycine

Product 1

HCID 66842904HCID 66842904, compoundYield 0%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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 (0.05 g, 0.092 mmol) and N-methyl morpholine (0.037 g, 0.37 mmol) in DMF (2 ml), under an atmosphere of nitrogen, was added TBTU (0.039 g, 0.12 mmol). After 1.5 h, 3-cyclopentyl-D-alanine (0.022 g, 0.139 mmol) was added. The reaction was allowed to stir for 1 h after which water (1 ml) was added. After 10 minutes, MeOH (2 ml) and NaBH4 (0.035 g, 0.925 mmol) were added. Full conversion to the corresponding alcohol was achieved within 5 minutes. The reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml) and the product was isolated by preparative HPLC of the mixture (eluent 0-50% CH3CN in 0.1M NH4OAc buffer). Freeze drying of pure fractions afforded the desired compound (0.031 g, 49%) as a colourless solid. m/z: 680.7 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 0.97-1.10 (m, 2H), 1.38-1.81 (m, 9H), 2.84-2.94 (m, 2H), 3.77 (d, 2H), 4.11-4.16 (m, 1H), 4.25-4.28 (m, 1H), 4.51 (s, 2H), 4.69-4.75 (m, 1H), 5.03-5.06 (m, 1H), 6.97-7.37 (m, 12H), 8.02-8.06 (m, 1H), 8.22 (t, 1H).

Workup

  1. additionwas added
  2. waitAfter 10 minutes
  3. customThe reaction was quenched by the addition of 0.1M NH4OAc buffer (2 ml)

Sources & evidence

ORD record
ord-12522304cbd540afa97209b797627080
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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