Hydrochloric Acid → 4-(4-Chloro-3-fluorobenzyl)morpholine

HRID 1924016

Reaction equation

HRID 1924016 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[F:10].[NH:11]1[CH2:16][CH2:15][O:14][CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl>ClC(Cl)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[CH:4][C:3]=1[F:10]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8083MorpholineHCID 27249854-Chloro-3-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 595438604-(4-Chloro-3-fluorobenzyl)morpholineYield 60.4%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

4-Chloro-3-fluorobenzaldehyde (1.0 g, 6.31 mmol), morpholine (0.546 ml, 6.31 mmol) and sodium triacetoxyborohydride (1.938 g, 9.14 mmol) were mixed in dichloroethane (19 ml) and the reaction stirred at ambient temperature under an atmosphere of argon over night. 1M HCl (aq, 25 ml) was added. The mixture was extracted with dichloromethane (×4). The pH was adjusted to ca 12 by adding KOH (s). The mixture was extracted with dichloromethane (×4). The combined organic phases were dried over MgSO4 filtered and concentrated in vacuo to give 4-(4-chloro-3-fluorobenzyl)morpholine (0.875 g, 60%) as a liquid.

Workup

  1. extractionThe mixture was extracted with dichloromethane (×4)
  2. additionby adding KOH (s)
  3. extractionThe mixture was extracted with dichloromethane (×4)
  4. dry with materialThe combined organic phases were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-5bff997b060e46a2b820e73238a8ebc3
Source dataset
uspto-grants-2012_05
Patent number
US08178529B2

Linked notes

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