Tetrabutylammonium Fluoride → HCID 131736916, compound

HRID 56382Notes

Reaction equation

HRID 56382 reaction equation
[Cl:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([O:10][CH3:11])=[C:4]([Cl:12])[C:3]=1[C:13]1[CH:14]=[C:15]2[C:20](=[CH:21][CH:22]=1)[N:19]=[C:18]([NH:23][C@H:24]1[C@@H:28]([NH:29]C(OCC[Si](C)(C)C)=O)[CH2:27][N:26]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:25]1)[N:17]=[CH:16]2.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CO.ClCCl>[NH2:29][C@@H:28]1[C@H:24]([NH:23][C:18]2[N:17]=[CH:16][C:15]3[C:20](=[CH:21][CH:22]=[C:13]([C:3]4[C:2]([Cl:1])=[C:7]([O:8][CH3:9])[CH:6]=[C:5]([O:10][CH3:11])[C:4]=4[Cl:12])[CH:14]=3)[N:19]=2)[CH2:25][N:26]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:27]1

Participants

6

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131736917HCID 131736917, compound

Product 1

HCID 131736916HCID 131736916, compoundYield 95.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of tert-butyl (3R,4S)-3-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)-4-(((2-(trimethylsilyl)ethoxy)carbonyl)amino)pyrrolidine-1-carboxylate (2.77 g, 4.1 mmol) and 1M TBAF in THF (6.1 mL, 6.1 mmol) was stirred in THF (27 mL) at 50° C. for 4 h and then 16 h at room temperature. The reaction mixture was diluted with 10% methanol in dichloromethane (100 mL) and washed with water (50 mL). The aqueous layer was then extracted with fresh dichloromethane (3×20 mL). The combined organic layers were washed with saturated brine solution, dried over sodium sulfate, filtered, concentrated down, and dried to yield tert-butyl (3S,4R)-3-amino-4-((6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-yl)amino)pyrrolidine-1-carboxylate as a yellow solid (2.1 g, 94%).

Workup

  1. custom16 h
  2. customat room temperature
  3. washwashed with water (50 mL)
  4. extractionThe aqueous layer was then extracted with fresh dichloromethane (3×20 mL)
  5. washThe combined organic layers were washed with saturated brine solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated down
  9. customdried

Sources & evidence

ORD record
ord-1470bf0119be4700a12768bfe64fcd34
Source dataset
uspto-grants-2016_09
Patent number
US09434700B2

Reaction notes

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