(2S)-2-amino-2-cyclopropylethan-1-ol → (2S)-2-((2R)-3-(4-Chloro-3-fluorophenyl)-2-(3-chlorophenyl)-3-hydroxypropyl)-N-((S)-1-cyclopropyl-2-hydroxyethyl)-2-methylpent-4-enamide

HRID 1846976Notes

Reaction equation

[CH2:1]([C@@:4]1([CH3:26])[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])=[C:19]([F:24])[CH:18]=2)[O:6][C:5]1=[O:25])[CH:2]=[CH2:3].[NH2:27][C@@H:28]([CH:31]1[CH2:33][CH2:32]1)[CH2:29][OH:30]>C(OCC)(=O)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]([CH:7]([OH:6])[C@@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[CH2:9][C@:4]([CH3:26])([CH2:1][CH:2]=[CH2:3])[C:5]([NH:27][C@@H:28]([CH:31]2[CH2:33][CH2:32]2)[CH2:29][OH:30])=[O:25])=[CH:18][C:19]=1[F:24]

Participants

Conditions

Temperature: 100 °C

Procedure

(3S,5R,6R)-3-Allyl-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one (32 g, 81 mmol, Example 4, Step E) was combined with (S)-2-amino-2-cyclopropylethanol (26.7 g, 265 mmol) and the suspension was heated at 100° C. overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with 1 N hydrochloric acid (2×), water, and brine. The organic layer was dried over magnesium sulfate and concentrated under vacuum to provide the title compound as a white solid.

Workup

temperatureThe reaction mixture was cooled to room temperature
washwashed with 1 N hydrochloric acid (2×), water, and brine
dry with materialThe organic layer was dried over magnesium sulfate
concentrationconcentrated under vacuum

Sources & evidence

ORD record: ord-5c225871a2424892855884a356f167df
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952036B2

Reaction notes

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