Tetrabutylammonium Fluoride → (+/-) Tert-butyl(2-chloro-5-cyano-3-(3-(hydroxymethyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate

HRID 921690Notes

Reaction equation

HRID 921690 reaction equation
[Si]([O:8][CH2:9][CH:10]1[N:15]([CH:16]2[CH2:19][O:18][CH2:17]2)[CH2:14][CH2:13][N:12]([C:20]2[C:21]([Cl:36])=[C:22]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH:23]=[C:24]([C:26]#[N:27])[CH:25]=2)[CH2:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[Cl:36][C:21]1[C:20]([N:12]2[CH2:13][CH2:14][N:15]([CH:16]3[CH2:19][O:18][CH2:17]3)[CH:10]([CH2:9][OH:8])[CH2:11]2)=[CH:25][C:24]([C:26]#[N:27])=[CH:23][C:22]=1[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34]

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86708559(+/-) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate

Product 1

HCID 86708560(+/-) Tert-butyl(2-chloro-5-cyano-3-(3-(hydroxymethyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamateYield 95.9%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(+/−) Tert-butyl (3-(3-(((tert-butyldimethylsilyl)oxy)methyl)-4-(oxetan-3-yl)piperazin-1-yl)-2-chloro-5-cyanophenyl)carbamate (551 mg, 1.026 mmol) was taken up in THF (5 mL) and TBAF (1.539 mL, 1.539 mmol) was added dropwise. The reaction was stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc and washed with water, then brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-100% 20% (2N NH3/MeOH)/DCM). (+/−) Tert-butyl (2-chloro-5-cyano-3-(3-(hydroxymethyl)-4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate (416 mg) was obtained as an orange glass.

Workup

  1. washwashed with water
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe material was purified by flash column chromatography (0-100% 20% (2N NH3/MeOH)/DCM)

Sources & evidence

ORD record
ord-2b7ae8c49b57426f8bb9bc1a098eaf3e
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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