Morpholine → Methyl 3fluoro-5-morpholino-7,8-dihydronaphthalene-2-carboxylate

HRID 1506458Notes

Reaction equation

HRID 1506458 reaction equation
[F:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][C:5]2[CH2:6][CH2:7][CH2:8][C:9](=O)[C:10]=2[CH:11]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>C1(C)C=CC=CC=1.[Ti](Cl)(Cl)(Cl)Cl>[F:1][C:2]1[C:3]([C:13]([O:15][CH3:16])=[O:14])=[CH:4][C:5]2[CH2:6][CH2:7][CH:8]=[C:9]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[C:10]=2[CH:11]=1

Participants

5

Reactant 2

HCID 8083MorpholineHCID 67170158HCID 67170158, compound

Product 1

HCID 67168691Methyl 3fluoro-5-morpholino-7,8-dihydronaphthalene-2-carboxylateYield 60%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 1140TolueneSolvent

Procedure

To a mixture of methyl 3fluoro-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (0.155 g, 0.698 mmol) and morpholine (0.304 mL, 3.49 mmol) in toluene (5.0 mL) at 0° C. was added titanium(IV) chloride (1M in toluene) (0.384 mL, 0.384 mmol) dropwise. The ice-bath was removed, and the orange, heterogeneous reaction mixture was stirred at room temperature for 16 hours. The heterogeneous, orange reaction mixture was filtered under reduced pressure through a pad of Celite which was then rinsed with toluene (3×10 mL). The pale yellow filtrate was concentrated under reduced pressure to give methyl 3fluoro-5-morpholino-7,8-dihydronaphthalene-2-carboxylate (0.122 g, 0.419 mmol, 60.0% yield). The product had an LC/MS M+1=292.2.

Workup

  1. customThe ice-bath was removed
  2. filtrationThe heterogeneous, orange reaction mixture was filtered under reduced pressure through a pad of Celite which
  3. washwas then rinsed with toluene (3×10 mL)
  4. concentrationThe pale yellow filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-d5e5b4de694445b3b6e38106bb51e508
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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