Morpholine → HCID 71513088, compound

HRID 2406304Notes

Reaction equation

HRID 2406304 reaction equation
[CH3:1][O:2][C:3]1[C:4]([N+:13]([O-:15])=[O:14])=[CH:5][C:6]([CH3:12])=[C:7]([CH:11]=1)[C:8]([OH:10])=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:49]1[CH2:54][CH2:53][O:52][CH2:51][CH2:50]1>C(Cl)Cl.O>[CH3:1][O:2][C:3]1[C:4]([N+:13]([O-:15])=[O:14])=[CH:5][C:6]([CH3:12])=[C:7]([C:8]([N:49]2[CH2:54][CH2:53][O:52][CH2:51][CH2:50]2)=[O:10])[CH:11]=1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 201618455-Methoxy-2-methyl-4-nitrobenzoic acid

Product 1

HCID 71513088HCID 71513088, compoundYield 94.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To 5-methoxy-2-methyl-4-nitrobenzoic acid (2.0 g, 9.47 mmol) in DCM (50 mL) was added DIPEA (8.3 mL, 47 mmol) and HATU (3.96 g, 10.4 mmol) followed by morpholine (0.83 mL, 9.47 mmol). The mixture was allowed to stir at RT for 5 h and then water (50 mL) and DCM (50 mL) were added. The aqueous phase was extracted with DCM (3×25 mL) and the combined organic phases were passed through a hydrophobic frit and the solvent was removed in vacuo. Purification of the residue via silica gel column chromatography (0-100% EtOAc in iso-hexane) gave (5-methoxy-2-methyl-4-nitrophenyl)(morpholino)methanone (2.5 g, 94%) as an off-white solid. LCMS (10 cm_ESCI_Formic_MeCN): [M+H]+=281 at 3.17 min. 1H NMR (400 MHz, CDCl3): δ 7.72 (s, 1H), 6.90 (s, 1H), 3.94 (s, 3H), 3.85-3.76 (m, 4H), 3.61 (dd, 2H), 3.23 (dd, 2H), 2.30 (s, 3H).

Workup

  1. extractionThe aqueous phase was extracted with DCM (3×25 mL)
  2. customthe solvent was removed in vacuo
  3. customPurification of the residue via silica gel column chromatography (0-100% EtOAc in iso-hexane)

Sources & evidence

ORD record
ord-a7284a7a4fd94d89b640eff084853ba5
Source dataset
uspto-grants-2014_08
Patent number
US08809331B2

Reaction notes

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