Potassium bis(trimethylsilyl)amide → [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[(5-bromobenzofuran-7-yl)methyloxy]piperidine

HRID 1602927Notes

Reaction equation

HRID 1602927 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C@H:20]([OH:24])[C@@H:19]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[Br:31][C:32]1[CH:33]=[C:34]([CH2:41]Br)[C:35]2[O:39][CH:38]=[CH:37][C:36]=2[CH:40]=1>COCCOC.O>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH2:21][C@H:20]([O:24][CH2:41][C:34]2[C:35]3[O:39][CH:38]=[CH:37][C:36]=3[CH:40]=[C:32]([Br:31])[CH:33]=2)[C@@H:19]1[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

Participants

6

Reactant 3

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 10901890(2S,3S)-1-t-Butyloxycarbonyl-3-hydroxy-2-phenylpiperidineHCID 196085405-Bromo-7-bromomethylbenzofuran

Product 1

HCID 57239557[2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[(5-bromobenzofuran-7-yl)methyloxy]piperidineYield 48.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

Potassium bis(trimethylsilyl)amide (300 mg) was added to a stirred solution of [2S,3S]-N-tert-butoxycarbonyl-2-phenylpiperidine-3-ol (160 mg) in dry 1,2-dimethoxyethane (3.0 ml) under a dry nitrogen atmosphere. After 30 minutes 5-bromo-7-bromomethylbenzofuran (290 mg) was added, and the reaction stirred for 18 hours at room temperature. The resulting mixture was then diluted with water (50 ml), and extracted into ethyl acetate (2×50 ml). The organic layers were separated and washed with brine (20 ml), dried over MgSO4, filtered and the solvent removed under reduced pressure. Purification by MPLC (20% ethyl acetate/n-hexane), afforded [2S,3S]-1-tert-butoxycarbonyl-2-phenyl-3-[(5-bromobenzofuran-7-yl)methyloxy]piperidine as a yellow gum (136 mg). 1H NMR (360 MHz,CDCl3)δ1.43 (9H, s), 1.65 (2H, m), 1.92 (2H, m), 2.70 (1H, t d, J=7.2, 3.0 Hz), 3.74 (2H,m), 4.90 (2H, d, J=5.0 Hz), 5.74 (1H, br s), 6.71 (1H, d, J=1.0 Hz), 7.30-7.42 (4H, m), 7.58 (3H, m), 7.75 (1H, d, J=1.0 Hz); MS m/z CI+ 487 (M+H+).

Workup

  1. extractionextracted into ethyl acetate (2×50 ml)
  2. customThe organic layers were separated
  3. washwashed with brine (20 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customPurification by MPLC (20% ethyl acetate/n-hexane)

Sources & evidence

ORD record
ord-1ac02ae861834e52a5602f453c461099
Source dataset
uspto-grants-1999_11
Patent number
US05985896

Reaction notes

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