Water → tert-Butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylmethoxy)piperidine-1-carboxylate

HRID 1176594Notes

Reaction equation

HRID 1176594 reaction equation
[CH3:1][O:2][C:3]1[CH:55]=[CH:54][CH:53]=[CH:52][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][C:32]2[C:37]3[N:38](COCC[Si](C)(C)C)[C:39](=[O:43])[CH2:40][CH2:41][CH2:42][C:36]=3[CH:35]=[CH:34][CH:33]=2)=[CH:13][CH:12]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O.COC(C)(C)C>O1CCCC1>[CH3:1][O:2][C:3]1[CH:55]=[CH:54][CH:53]=[CH:52][C:4]=1[CH2:5][O:6][CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH:18]2[O:30][CH2:31][C:32]2[C:37]3[NH:38][C:39](=[O:43])[CH2:40][CH2:41][CH2:42][C:36]=3[CH:35]=[CH:34][CH:33]=2)=[CH:15][CH:16]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15413tert-Butyl methyl etherHCID 2724141Tetrabutylammonium Fluoride2×HCID 68503548tert-butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-oxo-1-(2-trimethylsilanylethoxymethyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylmethoxy)piperidine-1-carboxylate

Product 1

HCID 68635087tert-Butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylmethoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.345 g of tert-butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-(2-oxo-1-(2-trimethylsilanylethoxymethyl)-2,3,4,5-tetrahydro-1H-benzo[b]azepin-9-ylmethoxy)piperidine-1-carboxylate in 4 ml of tetrahydrofuran is admixed with 0.85 ml of a 1M solution of tetrabutylammonium fluoride in tetrahydrofuran. The reaction solution is heated to reflux over 4 hours. A further 0.85 ml of tetrabutylammonium fluoride solution is added and the reaction solution is subsequently heated to reflux over a further 20 hours. The reaction solution is cooled and admixed with 50 ml each of water and tert-butyl methyl ether. The aqueous phase is removed and extracted with 40 ml of tert-butyl methyl ether. The combined organic phases are washed with 40 ml of brine, dried over sodium sulphate, filtered and concentrated to dryness. The title compound is obtained as a yellow oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.25 (3:1 EtOAc-heptane); Rt=4.34.

Workup

  1. temperatureThe reaction solution is heated
  2. temperatureto reflux over 4 hours
  3. temperaturethe reaction solution is subsequently heated
  4. temperatureto reflux over a further 20 hours
  5. temperatureThe reaction solution is cooled
  6. customThe aqueous phase is removed
  7. extractionextracted with 40 ml of tert-butyl methyl ether
  8. washThe combined organic phases are washed with 40 ml of brine
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-5ef8d9917836464493ba001e9ae5eef9
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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