Hydrochloric Acid → (2S)-2-((2R)-2-(3-Chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-cyclopropyl-2-hydroxyethyl)-2-methylpent-4-enamide

HRID 1846969Notes

Reaction equation

HRID 1846969 reaction equation
[CH2:1]([C@@:4]1([CH3:25])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[O:6][C:5]1=[O:24])[CH:2]=[CH2:3].[NH2:26][C@@H:27]([CH:30]1[CH2:32][CH2:31]1)[CH2:28][OH:29].Cl>C(OC(C)C)(=O)C>[Cl:16][C:12]1[CH:11]=[C:10]([C@H:8]([CH:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[OH:6])[CH2:9][C@:4]([CH3:25])([CH2:1][CH:2]=[CH2:3])[C:5]([NH:26][C@@H:27]([CH:30]2[CH2:32][CH2:31]2)[CH2:28][OH:29])=[O:24])[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 55283785(2S)-2-amino-2-cyclopropylethan-1-olHCID 58573721(3S,5R,6R)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one

Product 1

HCID 86731818(2S)-2-((2R)-2-(3-Chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-cyclopropyl-2-hydroxyethyl)-2-methylpent-4-enamideYield 100.2%

Reagents, catalysts & solvents 1

HCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

(3S,5R,6R)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one (125.0 g, 333 mmol, Example 1, Step D) was added to (S)-2-amino-2-cyclopropylethanol (101 g, 999 mmol) and the reaction mixture was heated at 110° C. under argon for 25 hours. The reaction mixture was diluted with isopropyl acetate, cooled to room temperature, and 3 M hydrochloric acid (400 mL) was added slowly. The mixture was stirred at room temperature for 20 minutes, and the layers were separated. The organic layer was washed with 1 M hydrochloric acid (200 mL) and brine, then dried over magnesium sulfate, filtered and concentrated under a vacuum to provide the desired product as a brown oil (159 g).

Workup

  1. temperaturecooled to room temperature
  2. customthe layers were separated
  3. washThe organic layer was washed with 1 M hydrochloric acid (200 mL) and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under a vacuum

Sources & evidence

ORD record
ord-7e8e0ffbcd0d4b23b438579ea7d576f5
Source dataset
uspto-grants-2015_02
Patent number
US08952036B2

Reaction notes

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