1,2-Dichloroethane → HCID 87662900, compound

HRID 1272372Notes

Reaction equation

HRID 1272372 reaction equation
[CH3:1][C:2]([CH3:23])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([OH:12])=O)=[O:6])[CH3:3].Cl.[F:25][C:26]([F:38])([F:37])[C:27]1[N:28]=[CH:29][C:30]2[CH2:36][CH2:35][NH:34][CH2:33][C:31]=2[N:32]=1.C(Cl)CCl.CN1CCOCC1>C(#N)C>[CH3:23][C:2]([CH3:1])([O:4][C:5]([NH:7][C@H:8]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[C:17]([F:21])=[CH:16][C:15]=1[F:22])[CH2:9][C:10]([N:34]1[CH2:35][CH2:36][C:30]2[CH:29]=[N:28][C:27]([C:26]([F:38])([F:25])[F:37])=[N:32][C:31]=2[CH2:33]1)=[O:12])=[O:6])[CH3:3]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 7146288(R)-3-(tert-butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic acidHCID 18456518HCID 18456518, compound

Product 1

HCID 87662900HCID 87662900, compoundYield 84.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
5 °C

Procedure

A 1-L round bottom flask was charged with 15.5 g (46.5 mmol) of (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]4-(2,4,5-trifluorophenyl)butanoic acid and 160 mL of acetonitrile. To the resultant suspension was added 14.5 g (60.5 mmol) of amine hydrochloride from Step B. The mixture was cooled to 5° C. and 12 g (62.8 mmol) of EDC and 6.9 mL (62.8 mmol) of N-methylmorpholine were added. After 2 h, the reaction was judged to be complete by LC-MS analysis. The mixture was partitioned between 100 mL of water and 160 mL of ethyl acetate. The organic phase was washed sequentially with 100 mL of saturated aqueous sodium bicarbonate solution and 100 mL of brine, dried over sodium sulfate, and concentrated in vacuo. Purification by Biotage flash chromatography (silica gel, 30–60% ethyl acetate/hexane) gave 20.3 g of the title compound as a white foam. LC-MS 419.4 (M+1-BOC).

Workup

  1. customThe mixture was partitioned between 100 mL of water and 160 mL of ethyl acetate
  2. washThe organic phase was washed sequentially with 100 mL of saturated aqueous sodium bicarbonate solution and 100 mL of brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customPurification by Biotage flash chromatography (silica gel, 30–60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-3b35c34537a8484da0bd6d0232a11b13
Source dataset
uspto-grants-2007_04
Patent number
US07208498B2

Reaction notes

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