Triethylamine → 3-Fluoro-1-[2-(2-methoxy-4-nitrophenoxy)ethyl]pyrrolidine

HRID 1181359Notes

Reaction equation

Br[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=1[O:14][CH3:15].[F:16][CH:17]1[CH2:21][CH2:20][NH:19][CH2:18]1.C(N(CC)CC)C>CN(C=O)C.CCOC(C)=O>[F:16][CH:17]1[CH2:21][CH2:20][N:19]([CH2:2][CH2:3][O:4][C:5]2[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:6]=2[O:14][CH3:15])[CH2:18]1

Participants

Conditions

Temperature: 80 °C

Procedure

1-(2-Bromoethoxy)-2-methoxy-4-nitrobenzene (0.2346 g, 0.8499 mmol) and 3-fluoropyrrolidine (0.3187 g, 2.5496 mmol) were combined in DMF (5 mL). Triethylamine (0.43 g, 4.2495 mmol) was added. The reaction was heated to 80° C. and stirred for 18 h. The reaction was cooled to RT and diluted with EtOAc (50 mL). The organics were washed with water (3×100 mL), dried over MgSO4, filtered and concentrated. The residue was purified by chromatatron (98:2 CH2Cl2:MeOH). The product was subjected to hydrogenation using 10% Pd/C under 1 atm of H2. The reaction was stirred for 18 h and was then filtered through celite and the celite washed with EtOAc (2×10 mL). The organics were concentrated to give 0.0442 g (0.1740 mmol, 20%) of the product. 1H NMR (CDCl3) δ 6.75 (d, 1H, J=8.4 Hz), 6.28 (s, 1H), 6.19 (d, 1H, J=8.3 Hz), 5.26-5.13 (m, 1H), 4.10 (t, 2H, J=5.7 Hz), 3.80 (s, 3H), 3.10-2.78 (m, 6H), 2.27-2.05 (m, 2H).

Workup

temperatureThe reaction was cooled to RT
washThe organics were washed with water (3×100 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by chromatatron (98:2 CH2Cl2:MeOH)
stirringThe reaction was stirred for 18 h
filtrationwas then filtered through celite
washthe celite washed with EtOAc (2×10 mL)
concentrationThe organics were concentrated

Sources & evidence

ORD record: ord-937c023ccb5044e7a6d6bb876480d565
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07285557B2

Reaction notes

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