Tetrabutylammonium Fluoride → (S)-3-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 519155Notes

Reaction equation

HRID 519155 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@:10]([CH3:38])([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][CH:27]=2)[O:24][CH2:23][C:22]2[N:17]3[CH:18]([CH3:37])[C:19](=[O:36])[N:20](COCC[Si](C)(C)C)[N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@:10]([CH3:38])([NH:13][C:14]2[CH:15]=[C:16]3[C:25](=[CH:26][CH:27]=2)[O:24][CH2:23][C:22]2[N:17]3[CH:18]([CH3:37])[C:19](=[O:36])[NH:20][N:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86727547(S)-3-methyl-3-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86727548(S)-3-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 54%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-3-methyl-3-[4-methyl-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.1 g, 2.016 mmol) in a solution of TBAF in THF (1 M, 20 mL, 20 mmoL) was stirred at 80° C. overnight. The reaction mixture was cooled to ambient temperature and diluted with water (25 mL). The aqueous solution was extracted with EtOAc (3×25 mL). The combined organic phase was washed with brine (10 mL), dried over sodium sulfate and filtered. The filtrate was concentrate in vacuo to give the residue, which was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum) to give (S)-3-methyl-3-(4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.45 g, 54%). 1H NMR (400 MHz, CDCl3) δ 8.19-8.05 (m, 1H), 6.94-6.77 (m, 1H), 6.53-6.23 (m, 2H), 4.74-4.46 (m, 3H), 3.62-3.30 (m, 4H), 2.32-2.17 (m, 1H), 2.00-1.86 (m, 1H), 1.59-1.44 (m, 15H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. extractionThe aqueous solution was extracted with EtOAc (3×25 mL)
  3. washThe combined organic phase was washed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrate in vacuo
  7. customto give the residue, which
  8. customwas purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum)

Sources & evidence

ORD record
ord-c599a7d24ec34ad899cd5cf08994fd37
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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