Hydrochloric Acid → HCID 11456682, compound

HRID 227547Notes

Reaction equation

HRID 227547 reaction equation
[F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([N:16]2[CH2:21][CH2:20][O:19][C@:18]([CH2:30][CH2:31][OH:32])([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)[CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CN(C1C=CC=CN=1)C.C(N(CC)CC)C.[CH3:51][C:52]1[CH:57]=[CH:56][C:55]([S:58](Cl)(=[O:60])=[O:59])=[CH:54][CH:53]=1.Cl>C(Cl)Cl.O>[CH3:51][C:52]1[CH:57]=[CH:56][C:55]([S:58]([O:32][CH2:31][CH2:30][C@:18]2([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=3)[O:19][CH2:20][CH2:21][N:16]([C:14](=[O:15])[CH2:13][C:5]3[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=[C:3]([C:2]([F:1])([F:33])[F:34])[CH:4]=3)[CH2:17]2)(=[O:60])=[O:59])=[CH:54][CH:53]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 86612947(2R)-2-[4-{[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 11456682HCID 11456682, compoundYield 60.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of (2R)-2-[4-{[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol obtained in Reference Example 1 (3.0 g, 5.7 mmol) in methylene chloride (30 ml) were added dimethylaminopyridine (0.07 g, 0.57 mmol) and triethylamine (1.2 ml, 8.5 mmol) under a nitrogen stream, the resulting mixture was cooled to 0-5° C., and then a solution of 4-methylbenzenesulfonyl chloride (1.3 g, 6.8 mmol) in methylene chloride (10 ml) was further added dropwise at below 10° C. with stirring. After the resulting mixture was stirred at room temperature for 8 hours, to the reaction mixture were added water (30 ml) and concentrated hydrochloric acid (1 ml), and the resulting mixture was partitioned. The separated organic layer was washed with water (30 ml) and evaporated to dryness. The residue obtained was purified by chromatography on a silica gel column and then crystallized from a mixed solvent of toluene (7 ml) and methylcyclohexane (35 ml) under ice-cooling to afford the title compound [2.3 g, yield: 60.3%] as a colorless crystalline solid.

Workup

  1. stirringAfter the resulting mixture was stirred at room temperature for 8 hours, to the reaction mixture
  2. customthe resulting mixture was partitioned
  3. washThe separated organic layer was washed with water (30 ml)
  4. customevaporated to dryness
  5. customThe residue obtained
  6. customwas purified by chromatography on a silica gel column
  7. customcrystallized from a mixed solvent of toluene (7 ml) and methylcyclohexane (35 ml) under ice-
  8. temperaturecooling

Sources & evidence

ORD record
ord-e6c89d1e2807496297c696480a17fe39
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

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