Morpholine → HCID 57386559, compound

HRID 420265Notes

Reaction equation

C(OC([C:7]1([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25]([F:32])[CH:24]=2)[C:12](=[O:13])[CH:11]([NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10][S:9][CH2:8]1)=O)C=C.N1CCOCC1.C([O-])(O)=O.[Na+]>C1COCC1>[C:18]([O:17][C:15](=[O:16])[NH:14][C@@H:11]1[C:12](=[O:13])[C@H:7]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[C:25]([F:32])[CH:24]=2)[CH2:8][S:9][CH2:10]1)([CH3:21])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 25 °C

Procedure

To a degassed solution of 5-tert-butoxycarbonylamino-3-(3-fluoro-4-nitro-benzyl)-4-oxo-tetra-hydro-thiopyran-3-carboxylic acid allyl ester (3.56 g, 7.6 mmol) and morpholine (1.4 mL, 15.2 mmol) in THF (50 mL) was added under argon Pd(PPh3)4 (0.092 g, 0.076 mmol) and the reaction mixture was stirred at 25° C. for 3 h. The reaction mixture was poured onto cold saturated NaHCO3 solution and extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4 and evaporated. The residue was re-dissolved in THF (10 mL) and kept at 25° C. for 3 h after addition of a catalytic amount of DBU. The title compound was obtained after evaporation and crystallization from diisopropylether as single diastereoisomer: TLC (hexane-EtOAc 1:2) Rf=0.38; HPLC RtA=2.17 min; ESIMS [M+NH4]+=402; 1H NMR (400 MHz, CDCl3): δ 8.0 (dd, 1H), 7.14 (m, 2H), 5.68 (m, 1H), 4.54 (m, 1H), 3.41 (m, 1H), 3.28 (dd, 1H), 3.14 (m, 1H), 2.84 (ddd, 1H), 2.69 (dd, 1H), 2.65 (m, 2H), 1.42 (s, 9H).

Workup

extractionextracted with EtOAc
washCombined extracts were washed with brine
dry with materialdried over MgSO4
customevaporated
dissolutionThe residue was re-dissolved in THF (10 mL)
waitkept at 25° C. for 3 h
additionafter addition of a catalytic amount of DBU

Sources & evidence

ORD record: ord-acb3784f7b874f808f7a13895c6ec269
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093406B2

Reaction notes

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