1,8-Diazabicyclo(5.4.0)undec-7-ene → (R)-methyl 4-azido-3,4-dihydro-2H-chromene-7-carboxylate

HRID 2219872Notes

Reaction equation

HRID 2219872 reaction equation
O[C@@H:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[O:5][CH2:4][CH2:3]1.C1(P([N:30]=[N+:31]=[N-:32])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1.CCOC(C)=O>[N:30]([C@H:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([O:14][CH3:15])=[O:13])=[CH:9][CH:10]=2)[O:5][CH2:4][CH2:3]1)=[N+:31]=[N-:32]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 69007341(S)-methyl 4-hydroxychroman-7-carboxylate

Product 1

HCID 86604855(R)-methyl 4-azido-3,4-dihydro-2H-chromene-7-carboxylate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To a 3 L three-neck round-bottomed flask equipped with argon inlet/outlet, thermometer, and magnetic stirring was added (S)-methyl 4-hydroxychroman-7-carboxylate (71 g, 340 mmol) in 800 mL of toluene. The reaction vessel was cooled with a ice/salt bath, and treated with a solution of diphenylphosphoryl azide (88 mL, 407 mmol, Aldrich) in 200 mL toluene (internal temp.=−4° C.). After 10 min, a solution of 1,8-diazabicyclo[5.4.0]undec-7-ene (61 mL, 407 mmol, Aldrich) in toluene (350 mL) was added over 30 min (the internal temperature did not exceed 1 ° C.). The reaction mixture was warmed to room temp and stirred for 40 h. The reaction mixture was diluted with 800 mL EtOAc and washed with 1M H3PO4, water, 5% NaHCO3, and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (10:1 hexane-EtOAc) to provide the title compound. MS (+ion ESI) m/z=234 (MH+).

Workup

  1. customTo a 3 L three-neck round-bottomed flask equipped with argon inlet/outlet
  2. temperatureThe reaction vessel was cooled with a ice/salt bath
  3. customdid not exceed 1 ° C.
  4. stirringstirred for 40 h
  5. washwashed with 1M H3PO4, water, 5% NaHCO3, and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (10:1 hexane-EtOAc)

Sources & evidence

ORD record
ord-3f810f2318194771b042863ec8a2dd24
Source dataset
uspto-grants-2008_08
Patent number
US07414134B2

Reaction notes

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