Tetrabutylammonium Fluoride → (R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

HRID 1426898Notes

Reaction equation

HRID 1426898 reaction equation
[Si]([O:8][CH:9]1[CH2:13][N:12]([C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:16]3[N:15]=2)[C@@H:11]([C:28]2[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=2[O:35][CH3:36])[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.CCOC(C)=O>[F:34][C:32]1[CH:31]=[CH:30][C:29]([O:35][CH3:36])=[C:28]([C@H:11]2[CH2:10][CH:9]([OH:8])[CH2:13][N:12]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:16]3[N:15]=2)[CH:33]=1

Participants

5

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86691711(R)-ethyl 5-(4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 86691712(R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-ethyl 5-(4-(tert-butyldimethylsilyloxy)-2-(5-fluoro-2-methoxyphenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (as a mixture of the cis and trans isomers) (0.0487 g, 0.0946 mmol) in THF (1 mL) at 0° C. was added 1 M TBAF in THF (0.104 mL, 0.104 mmol). The reaction mixture was warmed to ambient temperature and stirred for 2.5 hours. The reaction mixture was diluted with EtOAc (10 mL), washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to afford the crude (R)-ethyl 5-(2-(5-fluoro-2-methoxyphenyl)-4-hydroxypyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (as a mixture of cis and trans isomers; 37.9 mg, 100% yield). LC/MS (ES+APCI) m/z=401.1 (M+H).

Workup

  1. washwashed with brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e4cd68b37ef04b9f9becec032f723799
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

Loading…