Morpholine → 4-(5-Ethyl-2-fluorophenyl)morpholine

HRID 2105034Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[CH:5]=[CH:4][C:3]=1[F:10].CC(C)([O-])C.[Na+].[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH2:8]([C:6]1[CH:5]=[CH:4][C:3]([F:10])=[C:2]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH:7]=1)[CH3:9]

Participants

Conditions

Temperature: 85 °C

Procedure

To Intermediate 228.1 (203 mg, 1.00 mmol), BINAP (39.8 mg, 0.06 mmol), sodium tert-butoxide (115.3 mg, 1.20 mmol), morpholine (105 μL, 1.2 mmol) and Pd2(dba)3 (27.5 mg, 0.03 mmol), was added 5 mL toluene. The reaction vial was sealed and stirred at 85° C. for 15 h. The mixture was filtered through a 1″ pad of silica gel, eluting with 20% EtOAc/hexanes. The crude product was purified by flash chromatography (0 to 20% EtOAc/hexanes gradient) to afford 185 mg of intermediate 230.1. LCMS (2 min gradient) RT=1.66 min, 210.3 (M+H)+.

Workup

customThe reaction
customvial was sealed
filtrationThe mixture was filtered through a 1″ pad of silica gel
washeluting with 20% EtOAc/hexanes
customThe crude product was purified by flash chromatography (0 to 20% EtOAc/hexanes gradient)

Sources & evidence

ORD record: ord-bffa3a62182847c88d9dd285eb1f1d2f
Source dataset: uspto-grants-2009_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07576098B2

Reaction notes

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