Tributylphosphine → (S)-tert-butyl 4-(3-(4-bromo-2-fluoro-5-methylphenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate

HRID 407984Notes

Reaction equation

HRID 407984 reaction equation
C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Br:30][C:31]1[C:57]([CH3:58])=[CH:56][C:34]([O:35][C@@H:36]([CH2:53][CH2:54]O)[C:37]([NH:39][CH:40]2[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:42][CH2:41]2)=[O:38])=[C:33]([F:59])[CH:32]=1>C1COCC1>[Br:30][C:31]1[C:57]([CH3:58])=[CH:56][C:34]([O:35][C@H:36]2[CH2:53][CH2:54][N:39]([CH:40]3[CH2:45][CH2:44][N:43]([C:46]([O:48][C:49]([CH3:50])([CH3:52])[CH3:51])=[O:47])[CH2:42][CH2:41]3)[C:37]2=[O:38])=[C:33]([F:59])[CH:32]=1

Participants

5

Reactant 3

HCID 13831TributylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 86688114(S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate

Product 1

HCID 86688115(S)-tert-butyl 4-(3-(4-bromo-2-fluoro-5-methylphenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylateYield 75.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Tributylphosphine (2.0 mL, 7.8 mmol) was added slowly to a degassed solution of di-tert-butyl diazene-1,2-dicarboxylate (1.8 g, 7.8 mmol) in dry THF (30 mL) at ambient temperature. The resulting mixture was stirred for 5 minutes, then added dropwise to a 0° C. solution of (S)-tert-butyl 4-(2-(4-bromo-2-fluoro-5-methylphenoxy)-4-hydroxybutanamido)piperidine-1-carboxylate (3.2 g, 6.5 mmol) in THF (30 mL). The reaction was allowed to stir at ambient temperature overnight. Another 1.2 equivalents of reagents (tributylphosphine, tert-butyl diazene-1,2-dicarboxylate, and THF, prepared in same fashion) was added to the reaction mixture, and the reaction was stirred overnight. The reaction was concentrated and purified over silica gel (35 to 50% EtOAc in hexanes) to afford (S)-tert-butyl 4-(3-(4-bromo-2-fluoro-5-methylphenoxy)-2-oxopyrrolidin-1-yl)piperidine-1-carboxylate (2.3 g, 4.9 mmol, 75% yield) as a white solid.

Workup

  1. stirringto stir at ambient temperature overnight
  2. stirringthe reaction was stirred overnight
  3. concentrationThe reaction was concentrated
  4. custompurified over silica gel (35 to 50% EtOAc in hexanes)

Sources & evidence

ORD record
ord-57e1a9e0b12a4b88951985b45ed01584
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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