Morpholine → 4-(2-Fluoro-5-nitrobenzyl)morpholine

HRID 1257198Notes

Reaction equation

HRID 1257198 reaction equation
CCN(C(C)C)C(C)C.[NH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1.Br[CH2:17][C:18]1[CH:23]=[C:22]([N+:24]([O-:26])=[O:25])[CH:21]=[CH:20][C:19]=1[F:27].CCOC(C)=O>C1COCC1>[F:27][C:19]1[CH:20]=[CH:21][C:22]([N+:24]([O-:26])=[O:25])=[CH:23][C:18]=1[CH2:17][N:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 103539672-(Bromomethyl)-1-fluoro-4-nitrobenzene

Product 1

HCID 867136374-(2-Fluoro-5-nitrobenzyl)morpholineYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A −20° C. mixture of DIEA (552 mg, 4.27 mmol) and morpholine (242 mg, 2.78 mmol) in THF (5 mL) was treated drop-wise with a solution of 2-(bromomethyl)-1-fluoro-4-nitrobenzene (500 mg, 2.137 mmol) in THF (5 mL) and stirred overnight as the cooling bath expired. The mixture was treated with EtOAc, washed with water, then brine, dried over Na2SO4 and concentrated to dryness to afford 4-(2-fluoro-5-nitrobenzyl)morpholine (414 mg, 81% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.30 (dd, J=6.2, 3.0 Hz, 1H), 8.21 (ddd, J=9.0, 4.4, 3.0 Hz, 1H), 7.48 (t, J=9.1 Hz, 1H), 3.61 (s, 2H), 3.56 (t, J=4.6 Hz, 4H), 2.40 (t, J=4.4 Hz, 4H); MS (ESI) m/z: 241.1 [M+H]+.

Workup

  1. washwashed with water
  2. dry with materialbrine, dried over Na2SO4
  3. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-524475b8ccd24aa1a2a6d5fcff832581
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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