4-Methylmorpholine → HCID 68424784, compound

HRID 254050Notes

Reaction equation

HRID 254050 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]([CH:73]1[CH2:77][CH2:76][CH2:75][CH2:74]1)[C:70]([OH:72])=[O:71].[BH4-].[Na+]>CN(C=O)C.CO.O>[CH:73]1([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:26]=[CH:25][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:38][CH:37]=2)[C:70]([OH:72])=[O:71])[CH2:77][CH2:76][CH2:75][CH2:74]1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 4311764Sodium borohydrideHCID 10351805(αR)-α-Aminocyclopentaneacetic 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 68424784HCID 68424784, compound

Reagents, catalysts & solvents 3

HCID 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 (0.035 g, 0.065 mmol) was dissolved in DMF (2 ml) at 30° C. N-Methyl morpholine (0.026 g, 0.259 mmol) and TBTU (0.027 g, 0.084 mmol) were added. After 1 h, (2R)-amino(cyclopentyl)acetic acid (0.014 g, 0.097 mmol) was added. The mixture was stirred for 1 h and water (1 ml) was added. After 10 minutes, MeOH (2 ml) and NaBH4 (0.037 g, 0.971 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 (0.018 g, 42%) as a colourless solid. M/z: 666.0 (M−1). 1H NMR [(CD3)2SO), 400 M] δ 1.19-1.62 (m, 8H), 2.09-2.19 (m, 1H), 2.83-2.95 (m, 2H), 3.78 (d, 2H), 4.06-4.10 (m, 1H), 4.25-4.30 (m, 1H), 4.51 (s, 2H), 4.68-4.75 (m, 1H), 5.03-5.06 (m, 1H), 6.97-7.37 (m, 12H), 7.95-8.00 (m, 1H), 8.22 (t, 1H).

Workup

  1. waitAfter 10 minutes

Sources & evidence

ORD record
ord-f682a45d86914cb4bf0faa271a85566e
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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