(S)-4-(2-(2-carboxyacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide → (S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-3-(cyclopropylmethoxy)benzyloxy)-3-oxopropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

HRID 1776489Notes

Reaction equation

HRID 1776489 reaction equation
[C:1]([CH2:4][C:5]([O:7][C@H:8]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH:26]([F:28])[F:27])=[C:21]([O:29][CH2:30][CH:31]2[CH2:33][CH2:32]2)[CH:20]=1)[CH2:9][C:10]1[C:15]([Cl:16])=[CH:14][N+:13]([O-:17])=[CH:12][C:11]=1[Cl:18])=[O:6])([OH:3])=[O:2].[CH:34]1([CH2:37][O:38][C:39]2[CH:44]=[C:43]([CH2:45]O)[CH:42]=[CH:41][C:40]=2[N:47]([S:55]([CH3:58])(=[O:57])=[O:56])[C:48](=[O:54])[O:49][C:50]([CH3:53])([CH3:52])[CH3:51])[CH2:36][CH2:35]1>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:50]([O:49][C:48]([N:47]([C:40]1[CH:41]=[CH:42][C:43]([CH2:45][O:2][C:1](=[O:3])[CH2:4][C:5]([O:7][C@H:8]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH:26]([F:28])[F:27])=[C:21]([O:29][CH2:30][CH:31]3[CH2:32][CH2:33]3)[CH:20]=2)[CH2:9][C:10]2[C:15]([Cl:16])=[CH:14][N+:13]([O-:17])=[CH:12][C:11]=2[Cl:18])=[O:6])=[CH:44][C:39]=1[O:38][CH2:37][CH:34]1[CH2:35][CH2:36]1)[S:55]([CH3:58])(=[O:56])=[O:57])=[O:54])([CH3:53])([CH3:51])[CH3:52]

Participants

5

Reactant 2

HCID 86679438(S)-4-(2-(2-carboxyacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxideHCID 86679440Tert-butyl 2-(cyclopropylmethoxy)-4-(hydroxymethyl)phenyl(methylsulfonyl)carbamate

Product 1

HCID 86679439(S)-4-(2-(3-(4-(N-(tert-butoxycarbonyl)-methylsulfonamido)-3-(cyclopropylmethoxy)benzyloxy)-3-oxopropanoyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of (S)-4-(2-(2-carboxyacetoxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide (50 mg, 0.099 mmol), tert-butyl 2-(cyclopropylmethoxy)-4-(hydroxymethyl)phenyl-(methylsulfonyl)-carbamate (73 mg, 0.2 mmol), DMAP (14.5 mg, 0.12 mmol), and ECD (57 mg, 0.3 mmol) in DMF (1.5 ml) was stirred at RT overnight. The reaction mixture was quenched with water, and the product was extracted with EtOAc. The organic phase was washed with HCl 1M, NaHCO3 sat. sol. and brine. The organic layer was dried over Na2SO4 and evaporated to dryness. The crude (70 mg) was used for the next step without any further purification.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionthe product was extracted with EtOAc
  3. washThe organic phase was washed with HCl 1M, NaHCO3 sat. sol. and brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. customevaporated to dryness
  6. customThe crude (70 mg) was used for the next step without any further purification

Sources & evidence

ORD record
ord-7f998f934b294e5795b6498f3ad3768f
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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