1,2-Dichloroethane → (R)-tert-butyl 3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylcarbamate

HRID 510177Notes

Reaction equation

HRID 510177 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH:13]([CH3:15])[CH3:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[F:17][C:18]([F:22])([F:21])[CH2:19][NH2:20].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>ClCCl.C(OCC)(=O)C>[CH3:14][CH:13]([CH3:15])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10](=[O:12])[NH:20][CH2:19][C:18]([F:22])([F:21])[F:17]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 97722,2,2-Trifluoroethylamine hydrochlorideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acid

Product 1

HCID 117628462(R)-tert-butyl 3-methyl-1-oxo-1-(2,2,2-trifluoroethylamino)butan-2-ylcarbamateYield 93.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (R)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (Aldrich, 10.0 g, 46.0 mmole), 2,2,2 trifluoroethyl amine hydrochloride (Aldrich Chemical) (7.48 g, 55.2 mmole), EDC (10.6 g, 55.2 mmole), HOBT (9.16 g, 60.0 mmole) and DIPEA (24.1 mL, 138 mmole) in dichloromethane (200 mL) was allowed to stir overnite at room temperature. The mixture was diluted with ethyl acetate (200 mL) washed with 1N HCl, (50 mL) followed by aq. sodium bicarbonate (200 mL) and then brine (100 mL). The organic was dried over sodium sulfate, filtered and concentrated in vacuo to give 12.81 g of solid.

Workup

  1. washwashed with 1N HCl, (50 mL)
  2. dry with materialThe organic was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-39895ba7406e44a68a6f17c613f7f25a
Source dataset
uspto-grants-2015_08
Patent number
US09096598B2

Reaction notes

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