1,2-Dibromoethane → HCID 66724955, compound

HRID 1799193Notes

Reaction equation

HRID 1799193 reaction equation
BrCCBr.[Li+].[Cl-:6].I[C:8]1[CH:13]=[C:12]([Cl:14])[CH:11]=[CH:10][C:9]=1[C@@H:15]1[CH2:19][NH:18][C:17](=[O:20])[CH2:16]1.[CH:21]([C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=1)[C:26]([O:28]C)=[O:27])=[O:22].C1C[O:36]CC1>O>[ClH:14].[NH2:18][CH2:19][C@@H:15]([C:9]1[CH:10]=[C:11]([Cl:6])[CH:12]=[CH:13][C:8]=1[CH:21]([OH:22])[C:23]1[CH:24]=[C:25]([CH:30]=[CH:31][CH:32]=1)[C:26]([OH:28])=[O:27])[CH2:16][C:17]([OH:20])=[O:36]

Participants

7

Reactant 5

HCID 78391,2-DibromoethaneHCID 8028Tetrahydrofuran4×HCID 433294Lithium ChlorideHCID 639145Methyl 3-formylbenzoateHCID 66724832HCID 66724832, compound

Product 1

HCID 66724955HCID 66724955, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a suspension of Mg turnings (0.61 g, 2.5 mmol) in dry THF (5 mL) was added 1,2-dibromoethane (0.45 mL, 2.5 mmol), followed by washing with THF (2×4 mL). Then, a pale yellow solution of Li2MnCl4 (derived from MnCl2 (0.94 g, 7.5 mmol) and LiCl (0.64 g, 15 mmol) in THF (2.0 mL) was added to the solid Mg with vigorous stirring. The reaction mixture turned dark black overnight and was stirred for 2 days under a N2 atmosphere. To a solution of (4R)-4-(2-iodo-4-chlorophenyl)pyrrolidin-2-one in THF (2 mL) was added a solution of activated Mn(0) in THF (3 mL) at room temperature and the mixture stirred for 2 h followed by the dropwise addition of methyl 3-formylbenzoate (0.6 mL, 0.6 mmol). The reaction mixture was heated to reflux for 1 hr before being cooled to room temperature. The mixture was then diluted with water and extracted with ethyl acetate (3×20 mL). The combined organic phases were washed with brine, dried over MgSO4, and concentrated in vacuo. The crude residue was heated overnight in a 6N HCl aq. solution at 90° C. and then cooled to room temperature and purified by HPLC purification to afford the title compound (12). 1H-NMR (400 MHz, CD3OD): δ 2.65-2.79 (m, 2H), 3.01-3.05 (dd, J=10.0, 4.0 Hz, 1H), 3.43-3.51 (m, 1H), 3.80 (m, 1H), 4.48-4.49 (d, J=4 Hz, 1H), 7.31-7.38 (m, 3H), 7.43-7.45 (d, J=2.4 Hz, 1H), 7.84 (m, 1H), 7.94-7.95 (d, J=2.0 Hz, 1H); MS (ESI) m/z 364.09 (M+H)+.

Workup

  1. washby washing with THF (2×4 mL)
  2. additionwas added to the solid Mg with vigorous stirring
  3. stirringthe mixture stirred for 2 h
  4. temperatureThe reaction mixture was heated
  5. temperatureto reflux for 1 hr
  6. extractionextracted with ethyl acetate (3×20 mL)
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. temperatureThe crude residue was heated overnight in a 6N HCl aq. solution at 90° C.
  11. temperaturecooled to room temperature
  12. custompurified by HPLC purification

Sources & evidence

ORD record
ord-05df9523187043d8b9258acf066f8fab
Source dataset
uspto-grants-2013_01
Patent number
US08344028B2

Reaction notes

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