Morpholine → HCID 685713, compound

HRID 2406315Notes

Reaction equation

HRID 2406315 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([OH:6])=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:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>ClCCl>[Br:1][C:2]1[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:3]=1[C:4]([N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1)=[O:6]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 27827892-Bromo-4,5-difluorobenzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 685713HCID 685713, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Bromo-4,5-difluorobenzoic acid (2.00 g, 8.44 mmol), DIPEA (2.18 g, 16.88 mmol) and HATU (3.85 g, 10.13 mmol) were stirred at room temperature for 20 min in dichloromethane (120 mL). Morpholine (0.88 g, 10.13 mmol) was added then the reaction was stirred for 2 hours. The dichloromethane was removed and the resulting residue was partitioned between ethyl acetate and water. The layers were separated and the aqueous phase extracted with ethyl acetate. The combined organic extracts were passed through a phase separation cartridge and concentrated. The resulting residue was purified via silica gel column chromatography (0-100% ethyl acetate/isohexane) to afford (2-Bromo-4,5-difluorophenyl)(morpholino)methanone (2.5 g, 97%). 1H NMR (400 MHz, CDCl3): δ 7.44 (dd, J=9.42, 6.99 Hz, 1H), 7.14 (dd, J=9.57, 7.88 Hz, 1H), 3.88-3.69 (m, 5H), 3.64-3.57 (m, 1H), 3.33-3.17 (m, 2H).

Workup

  1. customThe dichloromethane was removed
  2. customthe resulting residue was partitioned between ethyl acetate and water
  3. customThe layers were separated
  4. extractionthe aqueous phase extracted with ethyl acetate
  5. customThe combined organic extracts were passed through a phase separation cartridge
  6. concentrationconcentrated
  7. customThe resulting residue was purified via silica gel column chromatography (0-100% ethyl acetate/isohexane)

Sources & evidence

ORD record
ord-f3685b2764524fc0a7ade59f7945da11
Source dataset
uspto-grants-2014_08
Patent number
US08809331B2

Reaction notes

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