Ammonium Hydroxide → Tert-butyl 2-(6-((perfluorophenoxy)sulfonyl)naphthalen-1-yl)pyrrolidine-1-carboxylate

HRID 1473354Notes

Reaction equation

HRID 1473354 reaction equation
[N:1]1([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.C([Li])(CC)C.Br[C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH:21]=[CH:22][C:23]([S:29]([O:32][C:33]1[C:38]([F:39])=[C:37]([F:40])[C:36]([F:41])=[C:35]([F:42])[C:34]=1[F:43])(=[O:31])=[O:30])=[CH:24]2.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C.[OH-].[NH4+]>[Cl-].[Zn+2].[Cl-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1>[F:43][C:34]1[C:35]([F:42])=[C:36]([F:41])[C:37]([F:40])=[C:38]([F:39])[C:33]=1[O:32][S:29]([C:23]1[CH:24]=[C:25]2[C:20](=[CH:21][CH:22]=1)[C:19]([CH:2]1[CH2:3][CH2:4][CH2:5][N:1]1[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[CH:28][CH:27]=[CH:26]2)(=[O:31])=[O:30]

Participants

9

Reactant 5

HCID 14923Ammonium HydroxideHCID 643455N-Boc-pyrrolidineHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 86687354Perfluorophenyl 5-bromonaphthalene-2-sulfonate2×HCID 178418400CID 53628100

Product 1

HCID 86687397Tert-butyl 2-(6-((perfluorophenoxy)sulfonyl)naphthalen-1-yl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-30 °C

Procedure

A 250-mL round-bottom flask was charged with tert-butyl 1-pyrrolidinecarboxylate (1.679 ml, 9.58 mmol) and THF (47.9 ml) to give a clear solution. The flask was flushed with Ar (g), then cooled in a −30° C. dry ice-acetone bath for 10 min. Sec-butyllithium (1.4 M in cyclohexane) (6.84 ml, 9.58 mmol) was added dropwise over 2 min. The resulting mixture was stirred for 15 min, during which time the bath had warmed to −25° C., then zinc chloride (1M in diethyl ether) (7.18 ml, 7.18 mmol) was added dropwise. The cooling bath was removed. After 25 min, a solid mixture of perfluorophenyl 5-bromonaphthalene-2-sulfonate (Intermediate M, 2.17 g, 4.79 mmol), palladium(ii) acetate (0.108 g, 0.479 mmol), and tri-tert-butylphosphonium tetrafluoroborate (0.139 g, 0.479 mmol) was added in one portion. The resulting mixture was stirred overnight at room temperature. A 30% aq. ammonium hydroxide solution was added, and the mixture was stirred vigorously for 10 min. The mixture was then filtered through diatomaceous earth with the aid of ethyl acetate. The filtrate was washed with 0.5N aq. HCl, and the aq. layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (80-g Redi-Sep column, 0-30% EtOAc/Heptane) to give tert-butyl 2-(6-((perfluorophenoxy)sulfonyl)naphthalen-1-yl)pyrrolidine-1-carboxylate as a light yellow solid. LC/MS ionized for 488.2 (desired product—t-Bu). m/z (ESI) 488.3 (M+H)+.

Workup

  1. customto give a clear solution
  2. customThe flask was flushed with Ar (g)
  3. temperaturehad warmed to −25° C.
  4. customThe cooling bath was removed
  5. waitAfter 25 min
  6. additionwas added in one portion
  7. stirringThe resulting mixture was stirred overnight at room temperature
  8. stirringthe mixture was stirred vigorously for 10 min
  9. filtrationThe mixture was then filtered through diatomaceous earth with the aid of ethyl acetate
  10. washThe filtrate was washed with 0.5N aq. HCl
  11. extractionthe aq. layer was extracted with EtOAc
  12. washThe combined organic layers were washed with brine
  13. dry with materialdried over sodium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue was purified by chromatography on silica gel (80-g Redi-Sep column, 0-30% EtOAc/Heptane)

Sources & evidence

ORD record
ord-6f1ef6daf3694be180318f54750a1c6e
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

Loading…