Benzyl chloroformate → HCID 71542557, compound

HRID 1776635Notes

Reaction equation

HRID 1776635 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].Cl[C:29]([O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)=[O:30]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:32]([O:31][C:29]([O:10][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)[CH2:8][C:7]1[C:6]([Cl:26])=[CH:5][N+:4]([O-:27])=[CH:3][C:2]=1[Cl:1])=[O:30])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 2

HCID 10387Benzyl chloroformate2×HCID 71092687HCID 71092687, compound

Product 1

HCID 71542557HCID 71542557, compoundYield 56.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-hydroxyethyl)pyridine 1-oxide (160 mg, 0.381 mmol) was dissolved in DCM (20 ml), and DMAP (0.056 g, 0.539 mmol) was added followed by benzyl chloroformate (0.077 ml, 0.539 mmol). The reaction mixture was stirred at RT for 6 hours. Additional benzyl chloroformate (0.077 ml, 0.539 mmol) was added, and stirring was continued at RT overnight. The reaction mixture was diluted with DCM and washed with aqueous saturated NH4Cl solution (20 mL). The organic layer was dried over sodium sulfate and evaporated to dryness. The crude was purified by chromatography on silica gel cartridge (DCM:ethyl acetate=8:2) to give 0.120 g of desired compound. A further purification by trituration with ethanol (10 mL) was required to afford (S)-4-(2-(benzyloxycarbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)ethyl)-3,5-dichloropyridine 1-oxide as a white amorphous solid (0.101 g, 0.182 mmol, 47.9% yield, MS/ESI+554.01 [MH]+, [αD]=−6.9, c=0.68, DCM).

Workup

  1. stirringstirring
  2. waitwas continued at RT overnight
  3. washwashed with aqueous saturated NH4Cl solution (20 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customevaporated to dryness
  6. customThe crude was purified by chromatography on silica gel cartridge (DCM:ethyl acetate=8:2)

Sources & evidence

ORD record
ord-4bef66a1982643218ea6daafc8cce693
Source dataset
uspto-grants-2016_02
Patent number
US09265768B2

Reaction notes

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