1,2-Dichloroethane → HCID 86679587, compound

HRID 1776640Notes

Reaction equation

HRID 1776640 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][CH:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[OH:10].[C:28]([O:32][C:33]([NH:35][C@H:36]([CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[C:37](O)=[O:38])=[O:34])([CH3:31])([CH3:30])[CH3:29].C(Cl)CCl>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[C:28]([O:32][C:33]([NH:35][C@H:36]([CH2:40][C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:37]([O:10][C@H:9]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH:18]([F:20])[F:19])=[C:13]([O:21][CH2:22][CH:23]2[CH2:25][CH2:24]2)[CH:12]=1)[CH2:8][C:7]1[C:6]([Cl:26])=[CH:5][N+:4]([O-:27])=[CH:3][C:2]=1[Cl:1])=[O:38])=[O:34])([CH3:31])([CH3:29])[CH3:30]

Participants

7

Reactant 3

HCID 111,2-DichloroethaneHCID 637610Boc-D-phenylalanineHCID 67096104HCID 67096104, compound

Product 1

HCID 86679587HCID 86679587, compoundYield 40.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (5 g, 11.90 mmol), (R)-2-(tert-butoxycarbonylamino)-3-phenylpropanoic acid (4.73 g, 17.85 mmol), DMAP (1.599 g, 13.09 mmol), and EDC (4.56 g, 23.80 mmol) were dissolved in DMF (5 ml). The reaction was stirred at RT for 2 hours to achieve completion. The reaction mixture was diluted with water, and the precipitate was filtered, washed with water, dissolved in DCM and extracted with HCl 1N, Na2CO3 sat. sol. and brine. The organic phase was dried over Na2SO4 and concentrated under vacuum. The crude product was crystallized in EtOH to give 4-((S)-2-((R)-2-(tert-butoxycarbonylamino)-3-phenylpropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (3.2 g, 4.79 mmol, 40.3% yield).

Workup

  1. filtrationthe precipitate was filtered
  2. washwashed with water
  3. dissolutiondissolved in DCM
  4. extractionextracted with HCl 1N, Na2CO3 sat. sol. and brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customThe crude product was crystallized in EtOH

Sources & evidence

ORD record
ord-938098b6d13d4252b2014e4537099f1f
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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