Hydrochloric Acid → (2R)-2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethanol

HRID 227545Notes

Reaction equation

HRID 227545 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH2:15][CH2:16][OH:17])[O:14][CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(N(CC)CC)C.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([CH:33]=[C:34]([O:38][CH3:39])[C:35]=1[O:36][CH3:37])[C:30](Cl)=[O:31].Cl>C1(C)C=CC=CC=1.O.C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@:9]2([CH2:15][CH2:16][OH:17])[O:14][CH2:13][CH2:12][N:11]([C:30](=[O:31])[C:29]3[CH:28]=[C:27]([O:26][CH3:25])[C:35]([O:36][CH3:37])=[C:34]([O:38][CH3:39])[CH:33]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 78282Benzoyl chloride, 3,4,5-trimethoxy-HCID 10956756(2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 12042117(2R)-2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethanolYield 104.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
2.5 °C

Procedure

To a mixture of (2R)-2-[2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol (25 g, 90.3 mmol) and acetonitrile (125 ml), triethylamine (27.4 g, 271 mmol) was added under a nitrogen stream, the resulting mixture was cooled to 0-5° C., then a solution of 3,4,5-trimethoxybenzoyl chloride (21.24 g, 92.1 mmol) in toluene (100 ml) was further added dropwise at below 10° C., and then the mixture was stirred at 0-5° C. for one hour. After completion of the reaction, toluene (150 ml), water (125 ml) and concentrated hydrochloric acid (25 ml) were added to the reaction mixture, and the resulting mixture was partitioned. The separated organic layer was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and water, and concentrated to afford (2R)-2-[2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholin-2-yl]ethanol (44.4 g) as an oil.

Workup

  1. additionwas added under a nitrogen stream
  2. additionwere added to the reaction mixture
  3. customthe resulting mixture was partitioned
  4. washThe separated organic layer was washed successively with a saturated aqueous solution of sodium hydrogencarbonate and water
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d14ec9bb909849c6aea7a07340e91c86
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

Loading…