Thiomorpholine → 4-(2,6-Difluoro-4-nitrophenyl)thiomorpholine

HRID 1991250Notes

Reaction equation

HRID 1991250 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:10]([O-:12])=[O:11])[CH:5]=[C:6]([F:9])[C:7]=1F.C(N(CC)C(C)C)(C)C.[NH:22]1[CH2:27][CH2:26][S:25][CH2:24][CH2:23]1>C(#N)C>[F:9][C:6]1[CH:5]=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=[C:2]([F:1])[C:7]=1[N:22]1[CH2:27][CH2:26][S:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 67164Thiomorpholine2×HCID 81531DiisopropylethylamineHCID 27827931,2,3-Trifluoro-5-nitrobenzene

Product 1

HCID 120965924-(2,6-Difluoro-4-nitrophenyl)thiomorpholine

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of 3,4,5-trifluoronitrobenzene (5.00 g, 28.24 mmol) in acetonitrile (60 mL) is cooled to 0° C. and treated with N,N-diisopropylethylamine (7.38 mL, 42.35 mmol) followed by thiomorpholine (2.98 mL, 29.65 mmol). The ice bath is removed and the reaction mixture stirred at room temperature under nitrogen for approximately 24 h, during which additional thiomorpholine (0.1 eq) is added. The solvent is removed under reduced pressure, and the residue is diluted with ethyl acetate, washed with 1N hydrochloric acid (until the washings are acidic), saturated aqueous sodium bicarbonate and saline, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound, mp 104-105° C.

Workup

  1. customThe ice bath is removed
  2. additionis added
  3. customThe solvent is removed under reduced pressure
  4. additionthe residue is diluted with ethyl acetate
  5. washwashed with 1N hydrochloric acid (until the washings
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6e9e7a30cf32487abc8ce61764e33bf1
Source dataset
uspto-grants-2010_01
Patent number
US07645781B2

Reaction notes

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