1,2-Dichloroethane → HCID 89455315, compound

HRID 1776648Notes

Reaction equation

HRID 1776648 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:27]=[CH:26][C:16]([C:17]([O:19][C:20]([CH3:25])([CH3:24])[C:21]([OH:23])=[O:22])=[O:18])=[CH:15][C:14]=1[O:28][CH2:29][CH:30]1[CH2:32][CH2:31]1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[Cl:37][C:38]1[CH:39]=[N+:40]([O-:63])[CH:41]=[C:42]([Cl:62])[C:43]=1[CH2:44][C@@H:45]([C:47]1[CH:52]=[CH:51][C:50]([O:53][CH:54]([F:56])[F:55])=[C:49]([O:57][CH2:58][CH:59]2[CH2:61][CH2:60]2)[CH:48]=1)O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:27]=[CH:26][C:16]([C:17]([O:19][C:20]([CH3:25])([CH3:24])[C:21]([O:23][C@H:45]([C:47]2[CH:52]=[CH:51][C:50]([O:53][CH:54]([F:55])[F:56])=[C:49]([O:57][CH2:58][CH:59]3[CH2:60][CH2:61]3)[CH:48]=2)[CH2:44][C:43]2[C:42]([Cl:62])=[CH:41][N+:40]([O-:63])=[CH:39][C:38]=2[Cl:37])=[O:22])=[O:18])=[CH:15][C:14]=1[O:28][CH2:29][CH:30]1[CH2:31][CH2:32]1)[S:9]([CH3:12])(=[O:10])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687HCID 71092687, compoundHCID 89455849HCID 89455849, compound

Product 1

HCID 89455315HCID 89455315, compoundYield 30.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)benzoyloxy)-2-methylpropanoic acid (300 mg, 0.636 mmol) and EDC (366 mg, 1.909 mmol) in dry DCM (10 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (267 mg, 0.636 mmol) and DMAP (78 mg, 0.636 mmol) were added, and the resulting solution was stirred at RT for 2 days. The solvent was evaporated and the residue was portioned between ethyl acetate and water; the organic phase was washed with 0.5N HCl, aqueous sat. NaHCO3 and brine. The organic phase was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel (DCM/MeOH/32% NH4OH=95/5/0.5) to give (S)-4-(2-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)-3-(cyclopropylmethoxy)-benzoyloxy)-2-methylpropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide as a white powder (168 mg, 0.192 mmol, 30.2% yield, MS/ESI+873.4 [MH]+).

Workup

  1. additionwere added
  2. customThe solvent was evaporated
  3. washthe organic phase was washed with 0.5N HCl, aqueous sat. NaHCO3 and brine
  4. dry with materialThe organic phase was dried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe crude was purified by flash chromatography on silica gel (DCM/MeOH/32% NH4OH=95/5/0.5)

Sources & evidence

ORD record
ord-fb57e26952d94d9eaf7ca5ba79facfc2
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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