Triethylamine → (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((2S,3S)-2-hydroxypentan-3-yl)-2-methylpent-4-enamide

HRID 1048418Notes

Reaction equation

HRID 1048418 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].Cl.[NH2:27][C@@H:28]([CH2:32][CH3:33])[C@@H:29]([OH:31])[CH3:30].C(N(CC)CC)C>C(OCC)(=O)C>[Cl:16][C:12]1[CH:11]=[C:10]([C@H:8]([C@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[OH:6])[CH2:9][C@:4]([CH3:25])([CH2:1][CH:2]=[CH2:3])[C:5]([NH:27][C@@H:28]([CH2:32][CH3:33])[C@@H:29]([OH:31])[CH3:30])=[O:24])[CH:15]=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 58573721(3S,5R,6R)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-oneHCID 66552260(2S,3S)-3-aminopentan-2-ol hydrochloride

Product 1

HCID 66552261(S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((2S,3S)-2-hydroxypentan-3-yl)-2-methylpent-4-enamide

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

To a 10 mL round-bottom reaction flask was added (3S,5R,6R)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one (750 mg, 1.998 mmol), (2S,3S)-3-aminopentan-2-ol hydrochloride (837 mg, 6.00 mmol, reference: J. Org. Chem., 2003, 68 (26), 9948), and triethylamine (1966 μl, 13.99 mmol). The vessel was fitted with a reflux condensor and heated to 85 to 95° C. for 2 d. The reaction was cooled to RT and diluted with ethyl acetate and washed with 1N HCl (2×20 mL) and brine. The organic layer was dried over MgSO4, filtered, and concentrated. Purification by column chromatography using 40 to 50% ethyl acetate in hexanes afforded (S)-2-((2R,3R)-2-(3-chlorophenyl)-3-(4-chlorophenyl)-3-hydroxypropyl)-N-((2S,3S)-2-hydroxypentan-3-yl)-2-methylpent-4-enamide.

Workup

  1. customThe vessel was fitted with a reflux condensor
  2. temperatureThe reaction was cooled to RT
  3. washwashed with 1N HCl (2×20 mL) and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by column chromatography

Sources & evidence

ORD record
ord-927ff6a976e84fd0b8345ed2dca8d35b
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

Loading…