(2S)-2-(phenoxymethyl)oxirane → (2S)-1-[N-benzyl-(6,7,8,9-tetrahydro-1-hydroxy-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanol

HRID 1936963Notes

Reaction equation

HRID 1936963 reaction equation
[O:1]([CH2:8][C@H:9]1[O:11][CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:12]([NH:19][CH:20]1[CH2:26][CH2:25][CH2:24][C:23]2[C:27]([OH:31])=[CH:28][CH:29]=[CH:30][C:22]=2[CH2:21]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>ClCCl>[CH2:12]([N:19]([CH:20]1[CH2:26][CH2:25][CH2:24][C:23]2[C:27]([OH:31])=[CH:28][CH:29]=[CH:30][C:22]=2[CH2:21]1)[CH2:10][C@H:9]([OH:11])[CH2:8][O:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 1534345(2S)-2-(phenoxymethyl)oxiraneHCID 2733225Ytterbium triflateHCID 22462907N-benzyl-(1-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)amine

Product 1

HCID 70132831(2S)-1-[N-benzyl-(6,7,8,9-tetrahydro-1-hydroxy-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanolYield 89.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of (2S)-3-phenoxy-1,2-epoxypropane (300 mg) (IL FARMACO, 50 (10), 643 (1995)), N-benzyl-(1-hydroxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)amine (535 mg), and ytterbium(III) trifluoromethanesulfonate (372 mg) in dichloromethane (15 ml) was stirred at room temperature for 3 days and partitioned between ethyl acetate and aqueous sodium bicarbonate. The organic layer was separated, washed with brine, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed (dichloromethane-methanol) over silica gel (16 g) to afford (2S)-1-[N-benzyl-(6,7,8,9-tetrahydro-1-hydroxy-5H-benzocyclohepten-6-yl)amino]-3-phenoxy-2-propanol (747 mg) as a colorless oil.

Workup

  1. custompartitioned between ethyl acetate and aqueous sodium bicarbonate
  2. customThe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. customevaporated in vacuo
  6. customThe residue was chromatographed (dichloromethane-methanol) over silica gel (16 g)

Sources & evidence

ORD record
ord-4696756b08da4dec8ce0e7fcb5616f7d
Source dataset
uspto-grants-2002_05
Patent number
US06391915B2

Reaction notes

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