Morpholine → Bavisant

HRID 13561Notes

Reaction equation

HRID 13561 reaction equation
[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]([C:12]3[CH:19]=[CH:18][C:15]([CH:16]=O)=[CH:14][CH:13]=3)=[O:11])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1.[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].[OH-].[Na+]>ClCCCl.O>[CH:1]1([N:4]2[CH2:9][CH2:8][N:7]([C:10]([C:12]3[CH:19]=[CH:18][C:15]([CH2:16][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[CH:14][CH:13]=3)=[O:11])[CH2:6][CH2:5]2)[CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8083MorpholineHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 592181834-(4-Cyclopropyl-piperazine-1-carbonyl)-benzaldehyde

Product 1

HCID 16061509Bavisant

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 962WaterSolvent

Conditions

Temperature
10 °C

Procedure

To a solution of 4-(4-cyclopropyl-piperazine-1-carbonyl)-benzaldehyde (56.0 g) in 1,2-dichloroethane (550 mL) was added morpholine (37.8 mL) dropwise over 5 min. The mixture was cooled to 10° C. and was treated with NaBH(OAc)3 (64.3 g) in portions over 1 h. After a further 2 h, the mixture was warmed to room temperature, and a water bath was used to keep the temperature below 20° C. After 18 h, water (60 mL) was added while the temperature was kept under 20° C. by the addition of small amounts of ice. After 20 min, the mixture was basified to pH˜10 with 1 N NaOH (450 mL) and the mixture was stirred for 10 min. The layers were separated, and the organic layer was washed with 1 N NaOH (150 mL). The combined aqueous layers were extracted with CH2Cl2 (200 mL). The combined organic layers were washed with brine (200 mL), dried (Na2SO4), and concentrated to yield the title compound as pale yellow viscous oil.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. customa water bath was used
  3. customthe temperature below 20° C
  4. waitAfter 18 h
  5. additionwas kept under 20° C. by the addition of small amounts of ice
  6. waitAfter 20 min
  7. customThe layers were separated
  8. washthe organic layer was washed with 1 N NaOH (150 mL)
  9. extractionThe combined aqueous layers were extracted with CH2Cl2 (200 mL)
  10. washThe combined organic layers were washed with brine (200 mL)
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-053cb57a227f45349f30f2f334909b4f
Source dataset
uspto-grants-2010_06
Patent number
US07728129B2

Reaction notes

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