Phosphorus sulfide (P2S5) → 5-(6-Bromo-pyridin-2-yl)-5-methyl-morpholine-3-thione

HRID 538296Notes

Reaction equation

HRID 538296 reaction equation
[Br:1][C:2]1[N:7]=[C:6]([C:8]2([CH3:15])[NH:13][C:12](=O)[CH2:11][O:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:17]>N1C=CC=CC=1.Cl.CCOC(C)=O>[Br:1][C:2]1[N:7]=[C:6]([C:8]2([CH3:15])[NH:13][C:12](=[S:17])[CH2:11][O:10][CH2:9]2)[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 2

HCID 14817Phosphorus sulfide (P2S5)HCID 866680115-(6-Bromo-pyridin-2-yl)-5-methyl-morpholin-3-one

Product 1

HCID 866680135-(6-Bromo-pyridin-2-yl)-5-methyl-morpholine-3-thione

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 5-(6-bromo-pyridin-2-yl)-5-methyl-morpholin-3-one (4.65 g, 17.15 mmol) and P2S5 (4.57 g, 20.58 mmol) in pyridine (60 ml) was stirred at 80° C. under N2 for 6 h. The reaction mixture was cooled to rt and diluted with 0.5N aq. HCl and EtOAc. The phases were separated and the aq. phase was twice extracted with EtOAc. The combined org. phases were washed with brine, dried over Na2SO4, filtered and concentrated. The title compound was obtained as a pale yellow solid after flash chromatography on silica gel (cyclohexane/EtOAc 100:0 to 75:25). HPLC RtH4=0.89 min; ESIMS: 287, 289 [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 11.15 (s, 1H), 7.86-7.82 (m, 1H), 7.61 (dd, 1H), 7.39 (dd, 1H), 4.44-4.34 (d, 2H), 4.13 (d, 1H), 3.74 (d, 1H), 1.52 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. customThe phases were separated
  3. extractionthe aq. phase was twice extracted with EtOAc
  4. washphases were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-324315e69ecb46b79859763a45f6663e
Source dataset
uspto-grants-2014_10
Patent number
US08865712B2

Reaction notes

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