Methanol → HCID 66594849, compound

HRID 1091362Notes

Reaction equation

HRID 1091362 reaction equation
[CH2:1]([N:8]1[CH2:13][C@H:12]([C:14]2[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])[O:11][CH2:10][C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+].Cl[Si](C)(C)C.CO>O1CCCC1>[CH2:1]([N:8]1[CH2:9][CH2:10][O:11][C@@H:12]([C:14]2[CH:19]=[C:18]([Br:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])[CH2:13]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 6397ChlorotrimethylsilaneHCID 4148881Lithium borohydrideHCID 66594872HCID 66594872, compound

Product 1

HCID 66594849HCID 66594849, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (6S)-4-benzyl-6-(5-bromo-2-methoxyphenyl)-morpholin-3-one (67.2 g, 179 mmol) in tetrahydrofuran (200 ml) was added to an ice-cooled mixture of lithium borohydride (8.55 g, 393 mmol) and chlorotrimethylsilane (99.7 ml, 785 mmol) in tetrahydrofuran (500 ml) over 45 minutes and the solution was stirred at same temperature for one hour and then at room temperature for 5 hours. After careful addition of methanol (60 ml) to the ice-cooled solution, solvent was removed under reduced pressure and the residue in 10% aqueous sodium hydroxide (280 ml) was stirred at 90° C. for 3 hours. The solvents were removed under reduced pressure and the residue was partitioned between water and diethyl ether. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by silica gel column chromatography (hexane/ethyl acetate) gave (2S)-4-benzyl-2-(5-bromo-2-methoxyphenyl)-morpholine (46.1 g, 71%, 2 steps) as a yellow oil.

Workup

  1. temperaturecooled
  2. waitat room temperature for 5 hours
  3. temperaturecooled solution, solvent
  4. customwas removed under reduced pressure
  5. stirringthe residue in 10% aqueous sodium hydroxide (280 ml) was stirred at 90° C. for 3 hours
  6. customThe solvents were removed under reduced pressure
  7. customthe residue was partitioned between water and diethyl ether
  8. washThe organic layer was washed with water and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by silica gel column chromatography (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-843fd5a6033046c4b9921e188f79bec7
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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