Tetrabutylammonium Fluoride → HCID 86727611, compound

HRID 519194Notes

Reaction equation

HRID 519194 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])[O:25][CH2:24][C:23]2[N:18]3[CH:19]([CH3:45])[C:20](=[O:44])[N:21](COCC[Si](C)(C)C)[N:22]=2)[CH2:10][C@@H:9]1[CH3:46])=[O:7])([CH3:4])([CH3:3])[CH3:2].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([CH3:14])[N:11]([C:15]2[CH:16]=[C:17]3[C:26](=[CH:27][C:28]=2[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[F:35])[O:25][CH2:24][C:23]2[N:18]3[CH:19]([CH3:45])[C:20](=[O:44])[NH:21][N:22]=2)[CH2:10][C@@H:9]1[CH3:46])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86727609HCID 86727609, compound

Product 1

HCID 86727611HCID 86727611, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

(2S,5R)-4-[7-(2-Fluoro-phenyl)-4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.2 g, 0.306 mmol) was dissolved in tetrabutylammonium fluoride (1M in THF, 3.06 mL, 3.06 mmol) and the reaction mixture was heated at 80° C. overnight. The reaction mixture was cooled to ambient temperature and water (10 mL) was added. The reaction mixture was extracted with EtOAc (3×10 mL). The combined organic phase was washed with brine (3×10 mL) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 0-40% EtOAc in petroleum ether) to give (2S,5R)-4-[7-(2-fluoro-phenyl)-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-yl]-2,5-dimethyl-piperazine-1-carboxylic acid tert-butyl ester (0.112 g, 70%) as a solid. LC/MS (Table 1, Method 25) Rt=0.959 min.; MS m/z: 524 [M+H]+. 1H NMR (400 MHz, CDCl3): δ 8.15-8.08 (m, 1H), 7.42 (m, 1H), 7.35-7.29 (m, 1H), 7.22-7.10 (m, 2H), 6.95-6.91 (m, 1H), 6.52-6.46 (m, 1H), 4.76-4.72 (m, 1H), 4.65-4.54 (m, 2H), 4.35 (m, 1H), 3.45 (m, 1H), 3.33 (m, 1H), 2.85 (m, 1H), 2.69 (m, 1H), 2.60 (m, 1H), 1.52 (m, 3H), 1.49-1.32 (m, 9H), 1.24 (m, 3H), 0.81 (m, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionThe reaction mixture was extracted with EtOAc (3×10 mL)
  3. washThe combined organic phase was washed with brine (3×10 mL)
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography on silica gel (eluting with 0-40% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-ddfddca1b34d41528e96e6a0e4cb1123
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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