4-Methylmorpholine → HCID 66843103, compound

HRID 254049Notes

Reaction equation

HRID 254049 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.[NH2:68][C@H:69]([CH2:73][CH2:74][CH:75]1[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1)[C:70]([O-:72])=[O:71].[Na+].[BH4-].[Na+]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CO.O.CS(C)=O>[CH:75]1([CH2:74][CH2:73][C@@H:69]([NH:68][C:34](=[O:35])[CH2:33][NH:32][C:30](=[O:31])[CH2:29][O:28][C:27]2[CH:37]=[CH:38][C:24]([C@@H:9]3[C@@H:10]([S:13][CH2:14][CH:15]([C:17]4[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=4)[OH:16])[C:11](=[O:12])[N:8]3[C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:25][CH:26]=2)[C:70]([OH:72])=[O:71])[CH2:80][CH2:79][CH2:78][CH2:77][CH2:76]1

Participants

11

Reactant 5

HCID 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}glycineHCID 66842981HCID 66842981, compound

Product 1

HCID 66843103HCID 66843103, compound

Reagents, catalysts & solvents 5

HCID 74236Tetrabutylammonium BromideCatalystHCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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) was dissolved in DMF (2 ml) at 30° C. N-Methyl morpholine (0.034 g, 0.333 mmol) and TBTU (0.043 g, 0.133 mmol) were added. After 1 h, sodium (2R)-2-amino-4-cyclohexylbutanoate (0.039 g, 0.189 mmol), DMSO (2 ml) and tetrabutylammoniumbromide (0.004 g, 0.011 mmol) were added. The mixture was stirred for 1 h and water (1 ml) was added. After 1 h, MeOH (2 ml) and NaBH4 (0.084 g, 2.220 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 mixture was purified by preparative HPLC (eluent 0-50% CH3CN in 0.1M NH4OAc buffer). Freeze-drying of the pure fractions gave the title compound (0.034 g, 43%) as a colourless solid. M/z: 708.1 (M−1). 1H NMR [(CD3)2SO), 400 MHz] δ 0.75-1.62 (m, 15H), 2.82-2.99 (m, 2H), 3.68-3.78 (m, 2H), 3.90-3.96 (m, 1H), 4.23-4.35 (m, 1H), 4.50 (s, 2H), 4.69-4.75 (m, 1H), 5.01-5.07 (m, 1H), 6.95-7.39 (m, 12H), 7.68-7.80 (m, 1H), 8.20-8.34 (m, 1H).

Workup

  1. waitAfter 1 h

Sources & evidence

ORD record
ord-43e7d18a9b3943f6bec39d24413b68e1
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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