Chlorotrimethylsilane → (S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(cyclopent-1-en-1-yl)propanoate

HRID 58837Notes

Reaction equation

HRID 58837 reaction equation
C[Si](Cl)(C)C.[C:6]([O:10][C:11]([NH:13][C@@H:14]([CH2:19]I)[C:15]([O:17][CH3:18])=[O:16])=[O:12])([CH3:9])([CH3:8])[CH3:7].FC(F)(F)S(O[C:27]1[CH2:31][CH2:30][CH2:29][CH:28]=1)(=O)=O>CN(C=O)C.[Cl-].[Na+].O.[Zn].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:6]([O:10][C:11]([NH:13][C@@H:14]([CH2:19][C:27]1[CH2:31][CH2:30][CH2:29][CH:28]=1)[C:15]([O:17][CH3:18])=[O:16])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

8

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 10903591methyl (2R)-2-(((tert-butoxy)carbonyl)amino)-3-iodopropanoateHCID 11769877Trifluoro-methanesulfonic acid cyclopent-1-enyl ester

Product 1

HCID 11680590(S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-(cyclopent-1-en-1-yl)propanoateYield 72%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent3×HCID 57417360Sodium chloride; waterSolvent

Procedure

To a suspension of zinc (123 g, 1.90 mol) in DMF (500 mL) was added TMSCl (46 mL) dropwise. The mixture was stirred at ambient temperature for 45 min. The upper clear liquid was drained out and the residue was washed with DMF (2×200 mL). The resulting solid was re-suspended in DMF (200 mL) and the mixture was cooled to 0° C. A solution of (R)-methyl 2-((tert-butoxycarbonyl)amino)-3-iodopropanoate (104 g, 0.320 mol) in DMF (300 mL) was added. The mixture was stirred at 0° C. under nitrogen for 20 min. The upper clear liquid was drained out and added dropwise to a solution of cyclopent-1-en-1-yl trifluoromethanesulfonate (90 g, 0.37 mol) and Pd(dppf)Cl2 (3.9 g, 4.7 mmol) in DMF (500 mL). After addition, the reaction mixture was stirred at 50° C. under nitrogen overnight then cooled to ambient temperature. Brine (500 mL) was added and the resulting mixture was extracted with MTBE (3×300 mL). The organic layers were combined, washed with brine, and concentrated. The residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=100:1 to 40:1) to afford (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-(cyclopent-1-en-1-yl)propanoate as a viscous oil (62 g, 72% yield).

Workup

  1. washthe residue was washed with DMF (2×200 mL)
  2. temperaturethe mixture was cooled to 0° C
  3. stirringThe mixture was stirred at 0° C. under nitrogen for 20 min
  4. additionAfter addition
  5. stirringthe reaction mixture was stirred at 50° C. under nitrogen overnight
  6. temperaturethen cooled to ambient temperature
  7. extractionthe resulting mixture was extracted with MTBE (3×300 mL)
  8. washwashed with brine
  9. concentrationconcentrated
  10. customThe residue was purified by flash column chromatography on silica gel (petroleum ether/EtOAc=100:1 to 40:1)

Sources & evidence

ORD record
ord-23e71d1ad3724685973bcae8cbe74eb0
Source dataset
uspto-grants-2016_09
Patent number
US09434761B2

Reaction notes

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