Tetrabutylammonium Fluoride → Benzyl 4-{4-[3-(2,5-difluorophenoxy)propoxy]phenyl}-3-[4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

HRID 1176504Notes

Reaction equation

HRID 1176504 reaction equation
[F:1][C:2]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:17][CH:16]2[O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]3[O:41][CH2:40][C:39](=[O:42])[N:38]([CH2:43][CH2:44][O:45][Si](C(C)C)(C(C)C)C(C)C)[C:37]=3[CH:56]=2)=[CH:11][CH:10]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:1][C:2]1[CH:60]=[CH:59][C:58]([F:61])=[CH:57][C:3]=1[O:4][CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)=[O:22])[CH2:17][CH:16]2[O:31][CH2:32][C:33]2[CH:34]=[CH:35][C:36]3[O:41][CH2:40][C:39](=[O:42])[N:38]([CH2:43][CH2:44][OH:45])[C:37]=3[CH:56]=2)=[CH:11][CH:10]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 68501828HCID 68501828, compound

Product 1

HCID 68505178Benzyl 4-{4-[3-(2,5-difluorophenoxy)propoxy]phenyl}-3-[4-(2-hydroxyethyl)-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

The solution of 2.0 g of benzyl 4-{4-[3-(2,5-difluorophenoxy)propoxy]phenyl}-3-[3-oxo-4-(2-triisopropylsilanyloxyethyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate in 30 ml of tetrahydrofuran is admixed with 2.30 ml of tetrabutylammonium fluoride solution (1M in tetrahydrofuran) and stirred at 60° C. over 30 minutes. The reaction mixture is cooled, poured onto water (100 ml) and extracted with tert-butyl methyl ether (2×100 ml). The organic phases are washed with brine (1×100 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a white foam from the residue by means of flash chromatography (SiO2 60F). Rf=0.10 (1:1 EtOAc-heptane); Rt=5.43.

Workup

  1. temperatureThe reaction mixture is cooled
  2. additionpoured onto water (100 ml)
  3. extractionextracted with tert-butyl methyl ether (2×100 ml)
  4. washThe organic phases are washed with brine (1×100 ml)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-81f5acf96c464117aa0e0573c898dd0b
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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