Trifluoroacetic acid → N-[(1S,2S)-2-[(3R,5S,6R)-6-(2,2-dimethyl-propoxy)-5-methyl-morpholin-3-yl]-2-hydroxy-1-(3-hydroxy-benzyl)-ethyl]-acetamide trifluoroacetate

HRID 20467Notes

Reaction equation

[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].C(OC([N:15]1[C@@H:20]([C@@H:21]([OH:35])[C@@H:22]([NH:31][C:32](=[O:34])[CH3:33])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)[CH2:19][O:18][C@@H:17]([O:36][CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[C@@H:16]1[CH3:42])=O)(C)(C)C>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH3:40][C:38]([CH3:39])([CH3:41])[CH2:37][O:36][C@H:17]1[C@H:16]([CH3:42])[NH:15][C@@H:20]([C@@H:21]([OH:35])[C@@H:22]([NH:31][C:32](=[O:34])[CH3:33])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([OH:30])[CH:25]=2)[CH2:19][O:18]1

Participants

Reactant 2

HCID 6422Trifluoroacetic acid

HCID 68563074HCID 68563074, compound

Product 1

HCID 68563032N-[(1S,2S)-2-[(3R,5S,6R)-6-(2,2-dimethyl-propoxy)-5-methyl-morpholin-3-yl]-2-hydroxy-1-(3-hydroxy-benzyl)-ethyl]-acetamide trifluoroacetate

Procedure

Add trifluoroacetic acid (3 mL) to (2R,3S,5R)-5-[(1S,2S)-2-acetylamino-1-hydroxy-3-(3-hydroxy-phenyl)-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester (84 mg, 0.17 mmol). Stir 40 minutes and evaporate to give N-[(1S,2S)-2-[(3R,5S,6R)-6-(2,2-dimethyl-propoxy)-5-methyl-morpholin-3-yl]-2-hydroxy-1-(3-hydroxy-benzyl)-ethyl]-acetamide trifluoroacetate (115 mg). Add diisopropylethyl-amine (0.074 mL, 0.425 mmol) dropwise to an ice cold solution of N-[(1S,2S)-2-[(3R,5S,6R)-6-(2,2-dimethyl-propoxy)-5-methyl-morpholin-3-yl]-2-hydroxy-1-(3-hydroxy-benzyl)-ethyl]-acetamide (115 mg) and benzyl chloroformate (0.029 mL, 0.20 mmol) in tetrahydrofuran (4 mL). Stir 30 minutes and add an additional portion of diisopropylethylamine (0.074 mL) and benzyl chloroformate (0.025 mL). Stir 50 minutes and warm to ambient temperature, stir 10 minutes and dilute with saturated aqueous sodium chloride followed by ethyl acetate and 1N aqueous hydrochloric acid. Separate layers and wash organic phase with saturated aqueous sodium chloride, dry with magnesium sulfate. Purify on silica gel with dichloromethane/ethyl acetate mixtures to give the desired compound (69 mg) as a white foam. MS(ESI): m/z=529 [M+H]+.

Workup

customevaporate

Sources & evidence

ORD record: ord-1d9a20d92ea24d6d909236847603dd0f
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07745438B2

Reaction notes

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