4-Chlorophenol → HCID 58048612, compound

HRID 1696950Notes

Reaction equation

HRID 1696950 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@H:13]([OH:17])[CH:14]([CH3:16])[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:37][C:38]1[CH:43]=[CH:42][C:41](O)=[CH:40][CH:39]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>CC1CCCO1>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([C@@H:13]([O:17][C:41]2[CH:42]=[CH:43][C:38]([Cl:37])=[CH:39][CH:40]=2)[CH:14]([CH3:15])[CH3:16])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 58048613HCID 58048613, compound

Product 1

HCID 58048612HCID 58048612, compoundYield 10.8%

Reagents, catalysts & solvents 1

HCID 73012-MethyltetrahydrofuranSolvent

Procedure

(S)-3-((R)-1-hydroxy-2-methylpropyl)pyrrolidine-1-carboxylic acid t-butyl ester (35.0 g, 144 mmol, 1.0 eq.), triphenylphosphine (41.5 g, 158 mmol, 1.1 eq.), p-chlorophenol (37.0 g, 288 mmol, 2.0 eq.) and 2-methyl-tetrahydrofuran (300 mL) were combined and the vessel purged with nitrogen. Diisopropyl azodicarboxylate (31.2 mL, 1.1 eq.) was added slowly at room temperature over 2 hours. The mixture was then stirred at room temperature overnight. Hexanes (600 mL) were added and the resulting mixture was stirred at room temperature for 30 minutes. The phases were separated and the organic layer was washed with 1.0 M NaOH in water (600 mL), washed with diluted saturated aqueous NaCl (20 mL), then dried over Na2SO4 to yield the crude BOC-protected intermediate. Additional hexanes (50 mL) were added and the resulting mixture was stirred for 30 minutes. Solids were filtered off to yield the crude BOC-protected intermediate as a thick oil, which was then purified by silica gel chromatography (0-10-20% EtOAc in hexanes) to yield (S)-3-[(S)-1-(4-chlorophenoxy)-2-methylpropyl]pyrrolidine-1-carboxylic acid t-butyl ester (5.5 g).

Workup

  1. customthe vessel purged with nitrogen
  2. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  3. customThe phases were separated
  4. washthe organic layer was washed with 1.0 M NaOH in water (600 mL)
  5. washwashed with diluted saturated aqueous NaCl (20 mL)
  6. dry with materialdried over Na2SO4
  7. customto yield the crude BOC-
  8. stirringthe resulting mixture was stirred for 30 minutes
  9. filtrationSolids were filtered off
  10. customto yield the crude BOC-
  11. customwas then purified by silica gel chromatography (0-10-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-462fd860be9d467196b84b072ba7b860
Source dataset
uspto-grants-2012_04
Patent number
US08163794B2

Reaction notes

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