Ammonium Chloride → HCID 118021858, compound

HRID 575831Notes

Reaction equation

HRID 575831 reaction equation
[NH4+].[Cl-].[CH2:3]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH2:15])[CH:11]=2)[O:6]1)[CH3:4].C(C1CCC2C(=C(N)C=CC=2)O1)C.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>CO.C(Cl)Cl.[Fe]>[CH2:3]([CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([NH:15][S:30]([CH3:29])(=[O:32])=[O:31])[CH:11]=2)[O:6]1)[CH3:4]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 20798379HCID 20798379, compoundHCID 118021686HCID 118021686, compound

Product 1

HCID 118021858HCID 118021858, compoundYield 12%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
85 °C

Procedure

The mixture of the title compounds from Step 4 (600 mg) was suspended in MeOH (6 mL) and sat. NH4Cl solution (2 mL). Fe (810 mg, 14.5 mmol) was added and the mixture was heated to 85° C. for 2.5 h. It was then filtered and extracted with EtOAc. The organic layer was dried and concentrated under reduced pressure to give a crude mixture of 2-ethyl-3,4-dihydro-2H-chromen-6-amine and 2-ethyl-3,4-dihydro-2H-chromen-8-amine. This mixture was dissolved in DCM (10 mL) and TEA (0.8 mL) and methanesulfonyl chloride (400 mg, 3.50 mmol) were added. The mixture was stirred at rt for 1 h. It was then extracted with DCM (45 mL×2), dried over Na2SO4, filtered, concentrated under reduced pressure and purified by column chromatography (PE/EA 50:1 to 20:1 to 10:1) to give the title compound (190 mg, 12% for three steps) as a yellow solid. 1H NMR (300 MHz, CDCl3): δ 6.99-6.80 (m, 2H), 6.78 (d, J=8.7 Hz, 1H), 6.16 (s, 1H), 3.95-3.90 (m, 1H), 2.96 (s, 3H), 2.83-2.76 (m, 2H), 2.04-1.97 (m, 1H), 1.81-1.64 (m, 3H), 1.05 (t, J=7.2 Hz, 3H). LCMS: 273 (M+NH4)+

Workup

  1. filtrationIt was then filtered
  2. extractionextracted with EtOAc
  3. customThe organic layer was dried
  4. concentrationconcentrated under reduced pressure
  5. customto give a crude
  6. extractionIt was then extracted with DCM (45 mL×2)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by column chromatography (PE/EA 50:1 to 20:1 to 10:1)

Sources & evidence

ORD record
ord-efaf3554ec3b4cef94ecdbea9d81a04e
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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