1,2-Dichloroethane → HCID 86679588, compound

HRID 1776643Notes

Reaction equation

HRID 1776643 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][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)[OH:10].C(Cl)CCl.[CH3:32][N:33]([C@H:43]([CH3:47])[C:44](O)=[O:45])[S:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)(=[O:36])=[O:35]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:27])[CH:5]=[C:6]([Cl:26])[C:7]=1[CH2:8][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)[O:10][C:44](=[O:45])[C@H:43]([N:33]([CH3:32])[S:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)(=[O:36])=[O:35])[CH3:47]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 86679589HCID 86679589, compound

Product 1

HCID 86679588HCID 86679588, compoundYield 70.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (397 mg, 0.945 mmol), EDC (362 mg, 1.891 mmol), and DMAP (289 mg, 2.364 mmol) in 10 ml of dry DCM was stirred for 15 minutes at room temperature, then (R)-2-(N-methylphenyl-sulfonamido)propanoic acid (345 mg, 1.418 mmol) was added. After stirring overnight at room temperature, the reaction was complete. The mixture was washed twice with 1N HCl, then with aq. NaHCO3, with brine and finally dried over sodium sulfate and evaporated to dryness. The residue was purified by flash chromatography on silica gel (AcOEt) to obtain 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((R)-2-(N-methylphenylsulfonamido)propanoyloxy)-ethyl)pyridine 1-oxide (430 mg, 0.666 mmol, 70.5% yield, MS/ESI+ 645.05 [MH]+, [αD]=+6.6, c=0.483, DCM).

Workup

  1. washThe mixture was washed twice with 1N HCl
  2. dry with materialwith aq. NaHCO3, with brine and finally dried over sodium sulfate
  3. customevaporated to dryness
  4. customThe residue was purified by flash chromatography on silica gel (AcOEt)

Sources & evidence

ORD record
ord-11099a92b4194a82befbca6a8f317a99
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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