Hydrochloric Acid → HCID 11433993, compound

HRID 227549Notes

Reaction equation

HRID 227549 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.[Cl: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>[Cl: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 73984-Chlorobenzenesulfonyl chlorideHCID 8471TriethylamineHCID 218852-DimethylaminopyridineHCID 186772052-[4-{[3,5-Bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol

Product 1

HCID 11433993HCID 11433993, compoundYield 47.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
2.5 °C

Procedure

To a solution of 2-[4-{[3,5-bis(trifluoromethyl)phenyl]acetyl}-2-(3,4-dichlorophenyl)morpholin-2-yl]ethanol obtained in Reference Example 2 (2.0 g, 3.8 mmol) in methylene chloride (20 ml) were added dimethylaminopyridine (0.05 g, 0.38 mmol) and triethylamine (0.8 ml, 5.7 mmol) under a nitrogen stream, the resulting mixture was cooled to 0-5° C., and then a solution of 4-chlorobenzenesulfonyl chloride (0.96 g, 4.5 mmol) in methylene chloride (6 ml) was further added dropwise at below 10° C. After stirring at 0-5° C. for 6 hours, water (20 ml) and concentrated hydrochloric acid (0.5 ml) were added to the reaction mixture, and the resulting mixture was partitioned. The separated organic layer was washed with water (20 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 ethyl acetate (2.4 ml) and methylcyclohexane (24 ml) under ice-cooling to afford the title compound [1.3 g, yield: 47.6%] as a colorless crystalline solid.

Workup

  1. customthe resulting mixture was partitioned
  2. washThe separated organic layer was washed with water (20 ml)
  3. customevaporated to dryness
  4. customThe residue obtained
  5. customwas purified by chromatography on a silica gel column
  6. customcrystallized from a mixed solvent of ethyl acetate (2.4 ml) and methylcyclohexane (24 ml) under ice-
  7. temperaturecooling

Sources & evidence

ORD record
ord-2276ccf8fd40477ab927356b2437943a
Source dataset
uspto-grants-2009_07
Patent number
US07560549B2

Reaction notes

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