Potassium Carbonate → HCID 9818557, compound

HRID 1108559Notes

Reaction equation

[C:1]([NH:4][CH2:5][CH:6]1[O:10][N:9]=[C:8]([C:11]2[CH:16]=[CH:15][C:14](F)=[C:13]([F:18])[CH:12]=2)[CH2:7]1)(=[O:3])[CH3:2].[C:19](=[O:22])([O-])[O-].[K+].[K+]>N1CCOCC1.C(Cl)Cl>[F:18][C:13]1[CH:12]=[C:11]([C:8]2[CH2:7][CH:6]([CH2:5][NH:4][C:1](=[O:3])[CH3:2])[O:10][N:9]=2)[CH:16]=[CH:15][C:14]=1[N:4]1[CH2:5][CH2:19][O:22][CH2:2][CH2:1]1

Participants

Conditions

Temperature: 140 °C

Procedure

To a resealable tube containing (+/-)-N-[[4,5-dihydro-3-(3,4-difluorophenyl)-5-isoxazolyl]methyl]acetamide (Step 3, Example 3) (1.70 g) in morpholine (5.83 mL) is added potassium carbonate (1.16 g) and heated to 140° C. for 48 hours. The reaction is diluted with CH2Cl2 (50 mL) and washed with H2O (3×50 mL) and saline (50 mL). The organic phase is dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh), eluting with methylene chloride/methanol (98.5/1.5). The appropriate fractions are combined (Rf =0.30, TLC, chloroform/methanol, 95/5) and concentrated in vacuo to give the title compound. The racemic material is separated on chiral HPLC (Chiralpak AD column, eluting with 8:2:1.5 heptane/isopropanol/chloroform) to give the individual enantiomers, the title compound having mp 179-180° C., [α]25D -71° (DMSO).

Workup

washwashed with H2O (3×50 mL) and saline (50 mL)
dry with materialThe organic phase is dried over sodium sulfate
concentrationconcentrated in vacuo
customchromatographed on silica gel (230-400 mesh)
washeluting with methylene chloride/methanol (98.5/1.5)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-19cc484fba4d451ba6e3459cfcefd0e5
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06069141

Reaction notes

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