Methyl chloroformate → 4-(3-(Dimethylamino)prop-1-ynyl)-2-methyl-5-nitrophenyl methyl carbonate

HRID 471945Notes

Reaction equation

HRID 471945 reaction equation
[C:1](=[O:16])([O:14][CH3:15])[O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6](Br)=[CH:5][C:4]=1[CH3:13].[CH3:17][N:18]([CH3:22])[CH2:19][C:20]#[CH:21].ClC(OC)=O>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(N(CC)CC)C.CN(C=O)C>[C:1](=[O:16])([O:14][CH3:15])[O:2][C:3]1[CH:8]=[C:7]([N+:9]([O-:11])=[O:10])[C:6]([C:21]#[C:20][CH2:19][N:18]([CH3:22])[CH3:17])=[CH:5][C:4]=1[CH3:13]

Participants

9

Reactant 3

HCID 6586Methyl chloroformateHCID 81643N,N-DimethylpropargylamineHCID 593950554-Bromo-2-methyl-5-nitrophenyl methyl carbonate

Product 1

HCID 593949884-(3-(Dimethylamino)prop-1-ynyl)-2-methyl-5-nitrophenyl methyl carbonateYield 20%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
100 °C

Procedure

To 4-bromo-2-methyl-5-nitrophenyl methyl carbonate (500 mg, 1.72 mmol), Pd(PPh3)2Cl2 (30 mg, 0.04 mmol), and CuI (3 mg, 0.02 mmol) were added DMF (5.0 mL), triethylamine (5.0 mL), and N,N-dimethylprop-2-yn-1-amine (717 mg, 919 μL, 8.62 mmol) under nitrogen atmosphere. The reaction mixture was heated under microwave irradiation at 100° C. for 15 min, resulting in product formation with partial loss of the carbonate group. The reaction was quenched with water and the aqueous layer was extracted with ethyl acetate, washed with 50% saturated NaHCO3 (2×20 mL), water, and brine. The solution was dried over Na2SO4, filtered, and dried down to a red oil. The oil was dissolved in cold (0° C.) dichloromethane (4 mL) and triethylamine (132 μL, 1.71 mmol) then treated dropwise with methyl chloroformate (132 μL, 1.71 mmol). After 5 min the reaction was quenched with water and the aqueous layer extracted with dichloromethane. The organic layer was dried over MgSO4, filtered and concentrated. Purification by silica gel chromatography (0-60% ethyl acetate/hexanes) provided 4-(3-(dimethylamino)prop-1-ynyl)-2-methyl-5-nitrophenyl methyl carbonate (100 mg, 20% yield). LC/MS m/z 293.3 [M+H]+.

Workup

  1. customresulting in product formation with partial loss of the carbonate group
  2. customThe reaction was quenched with water
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washwashed with 50% saturated NaHCO3 (2×20 mL), water, and brine
  5. dry with materialThe solution was dried over Na2SO4
  6. filtrationfiltered
  7. customdried down to a red oil
  8. customAfter 5 min the reaction was quenched with water
  9. extractionthe aqueous layer extracted with dichloromethane
  10. dry with materialThe organic layer was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by silica gel chromatography (0-60% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-1961ef5f26e84da7ae50757edcceea4c
Source dataset
uspto-grants-2014_01
Patent number
US08633189B2

Reaction notes

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