4-Methylmorpholine → Benzyl (2R)-2-Benzyl-3-(4-trifluoroethylpiperazin-1-ylcarbonyl)propionate

HRID 973498Notes

Reaction equation

[C:1]([CH2:4][C@@H:5]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])([OH:3])=O.CN1CCOCC1.ClC(OCC(C)C)=O.[F:38][C:39]([F:48])([F:47])[CH2:40][N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1>C(Cl)Cl>[CH2:16]([C@H:5]([CH2:4][C:1]([N:44]1[CH2:43][CH2:42][N:41]([CH2:40][C:39]([F:47])([F:48])[F:38])[CH2:46][CH2:45]1)=[O:3])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: -10 °C

Procedure

The resultant acid from Example 23 (0.500 g, 1.68 mmol) in CH2Cl2 (7 ml) at -10° C. was treated with N-methylmorpholine (0.20 ml, 1.82 mmol) and then isobutyl chloroformate (0.22 ml, 1.68 mmol). After 5 min 1-trifluoroethylpiperazine (0.30 g, 1.78 mmol) was added and the mixture was stirred at -10° C. for 15 min and then at room temperature for 2 h. The solvent was evaporated and the residue was taken up in ethyl acetate which was washed with saturated NaHCO3 solution, water and brine, and then dried over Na2SO4 and evaporated. Chromatography of the residue on silica gel with 20-33% ethyl acetate in hexane provided 0.61 g (81%) of an oil. 1H NMR (CDCl3) δ7.10-7.40 (m,10H), 5.15 (d,1H), 5.05 (d,1H), 3.25-3.70 (m,5H), 3.04 (dd,1H), 2.97 (q,2H), 2.81 (dd,1H), 2.72 (dd,1H), 2.60 (m,4H), 2.32 (dd,1H).

Workup

waitat room temperature for 2 h
customThe solvent was evaporated
washwas washed with saturated NaHCO3 solution, water and brine
dry with materialdried over Na2SO4
customevaporated

Sources & evidence

ORD record: ord-ff54ee1375de4638bbbcab286e398732
Source dataset: uspto-grants-1991_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05063208

Reaction notes

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