4-Isocyanato-1,2-dimethoxybenzene → HCID 86679582, compound

HRID 1776624Notes

Reaction equation

HRID 1776624 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].[N:28]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1)=[C:29]=[O:30]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[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:29](=[O:30])[NH:28][C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[C:33]([O:39][CH3:40])[CH:32]=1

Participants

5

Reactant 2

HCID 35178104-Isocyanato-1,2-dimethoxybenzeneHCID 71092687HCID 71092687, compound

Product 1

HCID 86679582HCID 86679582, compoundYield 70.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

To a stirred suspension of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (200 mg, 0.476 mmol) in anhydrous DCM (10 ml), a solution of DMAP (87 mg, 0.714 mmol) and 4-isocyanato-1,2-dimethoxybenzene (171 mg, 0.952 mmol) in anhydrous DCM (5 ml) was added dropwise within 10 minutes. The reaction mixture was stirred at RT overnight. After 18 hours, the reaction mixture was diluted with DCM (10 ml) and washed with HCl 0.5M. The organic layer was dried over Na2SO4 and evaporated. The crude material was purified by flash chromatography on silica gel (EtOAc 100%) affording the desired product as a white solid (200 mg, 0.334 mmol, 70.1% yield, [α]D=−27.6, c=0.45, DCM).

Workup

  1. waitAfter 18 hours
  2. washwashed with HCl 0.5M
  3. dry with materialThe organic layer was dried over Na2SO4
  4. customevaporated
  5. customThe crude material was purified by flash chromatography on silica gel (EtOAc 100%)

Sources & evidence

ORD record
ord-b9c851ca7c7c4059be411d28886e7933
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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