(+-)-Methionine → HCID 68226904, compound

HRID 718759Notes

Reaction equation

HRID 718759 reaction equation
[CH2:1]([C:3]12[CH2:19][CH2:18][C:17](=[O:20])[CH:16]=[C:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([O:14]C)[CH:11]=[CH:10][C:9]=12)[CH3:2].NC(C(O)=O)CCSC.CS(O)(=O)=O>C(Cl)Cl>[CH2:1]([C:3]12[CH2:19][CH2:18][C:17](=[O:20])[CH:16]=[C:4]1[CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=12)[CH3:2]

Participants

5

Reactant 3

HCID 876(+-)-MethionineHCID 6395Methanesulfonic AcidHCID 68227093HCID 68227093, compound2×

Product 1

HCID 68226904HCID 68226904, compoundYield 88.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture containing 11b-ethyl-9-methoxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one (10.2 g, 37.7 mmol) [prepared as described in US2012/238549 A1] and DL-methionine (18.3 g, 123 mmol) in methanesulfonic acid (100 mL, 1.54 mol) was mechanically stirred under nitrogen at rt over about 3 days. The reaction was diluted with DCM (700 mL) and poured carefully onto ice water (700 mL). The layers were separated and the aqueous layer was extracted again with DCM (500 mL). The combined organic layers were washed with water (2×500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (220 g) using a gradient from 0-50% EtOAc in DCM. Product fractions were combined and concentrated under reduced pressure to yield 11b-ethyl-9-hydroxy-1,2,5,6,7,11b-hexahydro-dibenzo[a,c]cyclohepten-3-one (17, R2=Ethyl) (8.54 g, 88%) as an off-white solid. LC/MS, method 1, 0.73 min, 319 (M+H)+. 1H NMR (400 MHz, DMSO) δ 9.19 (s, 1H), 7.11 (d, J=8.6 Hz, 1H), 6.62 (dd, J=8.5, 2.7 Hz, 1H), 6.51 (d, J=2.7 Hz, 1H), 5.81 (s, 1H), 2.79-2.70 (m, 1H), 2.67-2.52 (m, 1H), 2.44-2.35 (m, 2H), 2.33-2.18 (m, 3H), 2.14-2.04 (m, 1H), 2.01-1.90 (m, 1H), 1.86-1.66 (m, 3H), 0.78 (t, J=7.4 Hz, 3H).

Workup

  1. additionpoured carefully onto ice water (700 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted again with DCM (500 mL)
  4. washThe combined organic layers were washed with water (2×500 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified on silica gel (220 g)
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-03f9cc602ad548e591318bb64be6f13e
Source dataset
uspto-grants-2015_11
Patent number
US09193744B2

Reaction notes

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