Hydrochloric Acid → 8-Morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-amine

HRID 1487203Notes

Reaction equation

HRID 1487203 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]3[O:13][CH2:14][CH2:15][O:16][C:11]=3[C:10]([NH:17]C(=O)C)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.Cl>CO>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:12]3[O:13][CH2:14][CH2:15][O:16][C:11]=3[C:10]([NH2:17])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86699687N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetamide

Product 1

HCID 682847868-Morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-amineYield 60%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of N-(8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acetamide (2 g, 7.19 mmol) in methanol (100 mL) was added concentrated Hydrochloric acid (5 mL) and then the mixture was stirred at room temperature overnight. After the solvent was removed under reduce pressure, water was added and the pH was adjusted to 7-8 using aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate and the combined organic phases were dried over anhydrous sodium sulfate, concentrated to give a crude product, which was purified by silica gel column chromatography (petroleum ether/ethyl acetate 2/1) to afford the product 8-morpholino-2,3-dihydrobenzo[b][1,4]dioxin-5-amine (1 g, yield 60%). 1H NMR (400 MHz, CDCl3) δ ppm 6.38-6.41 (d, 1H, J=8.4 Hz), 6.27-6.29 (d, 1H, J=8.4 Hz), 4.28-4.32 (m, 4H), 3.85-3.88 (t, 4H, J=4.8 Hz), 3.55 (s, 2H), 2.95-2.97 (t, 4H, J=4.8 Hz).

Workup

  1. customAfter the solvent was removed
  2. additionwas added
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe combined organic phases were dried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto give a crude product, which
  7. customwas purified by silica gel column chromatography (petroleum ether/ethyl acetate 2/1)

Sources & evidence

ORD record
ord-4487b51164eb4c39886e126bac379a6b
Source dataset
uspto-grants-2016_08
Patent number
US09428508B2

Reaction notes

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