Morpholine → HCID 59138644, compound

HRID 1514077Notes

Reaction equation

Br[C:2]1[S:6][C:5]([CH:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=2)[C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:4][CH:3]=1.[NH:22]1[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:21][C:17]1[CH:16]=[C:15]([CH:7]([C:5]2[S:6][C:2]([N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:3][CH:4]=2)[C:8]([CH3:14])([CH3:13])[C:9]([O:11][CH3:12])=[O:10])[CH:20]=[CH:19][CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of methyl 3-(5-bromothiophen-2-yl)-3-(3-fluorophenyl)-2,2-dimethyl-propanoate, product of Preparation 1, Step 2, (367 mg, 0.988 mmol), morpholine (0.572 mL), palladium acetate (44 mg, 0.20 mmol), 2-(di-tert-butylphosphino)-biphenyl (118 mg, 0.40 mmol), and sodium tert-butoxide (228 mg, 2.37 mmol) in toluene (5 ml) was heated at 80° C. for 2 h. The reaction mixture was cooled to room temperature, the solid was removed by filtration, and the filtrate was concentrated in vacuo. The crude product was purified by silica gel flash chromatography using 20% ethyl acetate in hexanes to give methyl 3-(3-fluorophenyl)-2,2-dimethyl-3-(5-morpholinothiophen-2-yl)propanoate as an oil (120 mg, 32.2%). LC/MS (m/z) 378.33 [(M+H)+]; HPLC Rt: 3.548 min.

Workup

temperatureThe reaction mixture was cooled to room temperature
customthe solid was removed by filtration
concentrationthe filtrate was concentrated in vacuo
customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record: ord-ce14855ca2554454a265f00f3842403a
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08222247B2

Reaction notes

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