Morpholine → HCID 21049007, compound

HRID 2212391Notes

Reaction equation

HRID 2212391 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C([N:9]([CH2:12][CH3:13])CC)C.[S:14](Cl)(Cl)(=[O:16])=[O:15].[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([C:29]2([C:47]3[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:48]=3[F:54])[CH2:34]CC(CS(N3CCC[C@@H]3C(O)=O)(=O)=O)[CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1.CCN(C(C)C)C(C)C>ClCCl.C(OCC)(=O)C.O.C(#N)C>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([S:26]([C:29]2([C:47]3[CH:52]=[C:51]([F:53])[CH:50]=[CH:49][C:48]=3[F:54])[CH2:34][CH2:13][CH:12]([NH:9][S:14]([N:1]3[CH2:6][CH2:5][O:4][CH2:3][CH2:2]3)(=[O:16])=[O:15])[CH2:31][CH2:30]2)(=[O:28])=[O:27])=[CH:22][CH:21]=1

Participants

10

Reactant 5

HCID 8083MorpholineHCID 8471TriethylamineHCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 69583707HCID 69583707, compound

Product 1

HCID 21049007HCID 21049007, compoundYield 27.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of morpholine (200 μl, 2.3 mmol) and triethylamine (480 μL, 0.38 mmol) in dichloromethane (1 ml) was added dropwise to a solution of sulfuryl chloride (322 μL, 0.38 mmol) in dichloromethane (2 ml) at 0° C. After 1.25 hours the reaction was diluted with ethyl acetate and H2O, the organic layer washed with 2N HCl, dried (MgSO4) and evaporated to an oil which was taken up in acetonitrile (2 ml) and added to a solution of Intermediate R (100 mg, 0.26 mmol) in acetonitrile (2 ml) at room temperature, followed by Hünig's Base (100 μl, 0.52 mmol). Reaction was heated to 80° C. for 6 hours then diluted with ethyl acetate and washed with 2N sodium hydroxide, dried (MgSO4) and evaporated to a brown oil which was purified by chromatography, eluting with 20% ethyl acetate/hexane to obtain a white solid (38 mg). 1H NMR (360 MHz, CDCl3) δ 7.39–7.30 (4H, m), 7.09–7.04 (2H, m) 6.88–6.81 (1H, m), 4.50–4.48 (1H, d, J=6.6 Hz), 3.76–3.74 (4H, m), 3.58–3.56 (1H, m), 3.22–3.20 (4H, m), 2.43–2.35 (4H, m), 2.04–1.99 (2H, m), 1.57–1.50 (2H, m). m/z=533, 535 [MH]−

Workup

  1. washthe organic layer washed with 2N HCl
  2. dry with materialdried (MgSO4)
  3. customevaporated to an oil which
  4. customReaction
  5. washwashed with 2N sodium hydroxide
  6. dry with materialdried (MgSO4)
  7. customevaporated to a brown oil which
  8. customwas purified by chromatography
  9. washeluting with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-f98de5c752474d4a8c5d310fc2312a39
Source dataset
uspto-grants-2006_09
Patent number
US07101895B2

Reaction notes

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