1,2-Dichloroethane → HCID 131737064, compound

HRID 59742Notes

Reaction equation

HRID 59742 reaction equation
[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([C:18]([OH:20])=[O:19])[S:16][CH:17]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:21][C:22]1[CH:23]=[N+:24]([O-:47])[CH:25]=[C:26]([Cl:46])[C:27]=1[CH2:28][C@@H:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:40])[F:39])=[C:33]([O:41][CH2:42][CH:43]2[CH2:45][CH2:44]2)[CH:32]=1)O.C(Cl)CCl>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]([C:13]1[CH:14]=[C:15]([C:18]([O:20][C@H:29]([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH:38]([F:39])[F:40])=[C:33]([O:41][CH2:42][CH:43]3[CH2:44][CH2:45]3)[CH:32]=2)[CH2:28][C:27]2[C:26]([Cl:46])=[CH:25][N+:24]([O-:47])=[CH:23][C:22]=2[Cl:21])=[O:19])[S:16][CH:17]=1)[S:9]([CH3:12])(=[O:11])=[O:10])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 111,2-DichloroethaneHCID 71092687(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxideHCID 121461939HCID 121461939, compound

Product 1

HCID 131737064HCID 131737064, compoundYield 32.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(N-(tert-butoxycarbonyl)methylsulfonamido)-thiophene-2-carboxylic acid (Int. 44) (100 mg, 0.311 mmol) in DCM (5 ml), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (131 mg, 0.311 mmol), EDC (179 mg, 0.934 mmol) and DMAP (19.01 mg, 0.156 mmol) were added, and reaction was stirred at RT overnight. The mixture was diluted with DCM (10 ml) and washed with 1N HCl; the aqueous phase was extracted with EtOAc and the combined organic layers were dried over sodium sulfate. The solvent was removed under vacuum and the crude was purified by flash chromatography on silica gel (DCM/MeOH=98/2) affording (S)-4-(2-(4-(N-(tert-butoxycarbonyl)methylsulfonamido)thiophene-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (Int. 45) (72 mg, 0.100 mmol, MS/ESI+722.9 [MH]+).

Workup

  1. customreaction
  2. washwashed with 1N HCl
  3. extractionthe aqueous phase was extracted with EtOAc
  4. dry with materialthe combined organic layers were dried over sodium sulfate
  5. customThe solvent was removed under vacuum
  6. customthe crude was purified by flash chromatography on silica gel (DCM/MeOH=98/2)

Sources & evidence

ORD record
ord-54c7ef8deddb4156a0642058b192cc5c
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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