Acetonitrile → (S)-methyl 4-hydroxychroman-7-carboxylate

HRID 2219870Notes

Reaction equation

HRID 2219870 reaction equation
CC1C=CC(S(N[C@H]([C@@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1.[C:27]([C:31]1[CH:40]=[C:39]2[C:34]([C:35](=[O:41])[CH2:36][CH2:37][O:38]2)=[CH:33][CH:32]=1)([O:29][CH3:30])=[O:28].C(#N)C>C(O)(C)C>[OH:41][C@@H:35]1[C:34]2[C:39](=[CH:40][C:31]([C:27]([O:29][CH3:30])=[O:28])=[CH:32][CH:33]=2)[O:38][CH2:37][CH2:36]1

Participants

5

Reactant 3

HCID 6342AcetonitrileHCID 6612782(1S,2S)-(+)-N-p-Tosyl-1,2-diphenylethylenediamineHCID 11769654Methyl 4-oxochroman-7-carboxylate

Product 1

HCID 69007341(S)-methyl 4-hydroxychroman-7-carboxylate

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (1S,2S)-TsDPEN (1.709 g, 4.85 mmol) in isopropanol (5 mL) was added to a 35 mL schlenk-flask and cooled to 0° C. The solution was degassed by three cycles of evacuation/nitrogen refill. Then, [RuCl2(η6-p-cymene)]2 (1.313 g, 2.425 mmol) was added, followed by TEA (1.352 mL, 9.699 mmol). The reaction mixture was heated to 80° C. under N2 for 1 h and cooled. The iso-propanol was removed under a stream of nitrogen, and dissolved in 10 mL acetonitrile. The catalyst solution was added to nitrogen filled 1 L 3-N flask equipped with overhead stirring. 7-Carbomethoxy-4-chromanone (100 g, 485 mmol) and 400 mL acetonitrile was added to the flask, followed by 5:2 formic acid-TEA (50 mL). The reaction mixture was incubated for 24 h at 30° C. An additional portion of formic acid-TEA (5 mL) was added and the reaction mixture stirred for an additional 24 h. The solution was concentrated completely by rotary evaporation. The product was purified by crystallization from 200 mL 2-propanol and 100 mL hexanes. The solids were collected by filtration and washed with cold 2:1 iPrOH-Hex. Final drying of the solids afforded the title compound. MS (m/z): 208.9 (m+H). Chiral HPLC showed the enantiomeric purity to be greater than 98%, when compared to racemic material.

Workup

  1. customThe solution was degassed by three cycles of evacuation/nitrogen refill
  2. temperatureThe reaction mixture was heated to 80° C. under N2 for 1 h
  3. temperaturecooled
  4. customThe iso-propanol was removed under a stream of nitrogen
  5. dissolutiondissolved in 10 mL acetonitrile
  6. additionThe catalyst solution was added to nitrogen
  7. additionfilled 1 L 3-N flask
  8. customequipped with overhead stirring
  9. concentrationThe solution was concentrated completely by rotary evaporation
  10. customThe product was purified by crystallization from 200 mL 2-propanol and 100 mL hexanes
  11. filtrationThe solids were collected by filtration
  12. washwashed with cold 2:1 iPrOH-Hex
  13. customFinal drying of the solids

Sources & evidence

ORD record
ord-4f1943a9c1bb4a8ca4d5727e6b17f861
Source dataset
uspto-grants-2008_08
Patent number
US07414134B2

Reaction notes

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