Diisopropylethylamine → HCID 86603620, compound

HRID 226312Notes

Reaction equation

HRID 226312 reaction equation
C([N:8]1[CH2:12][CH2:11][C@@H:10]([N:13]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:14]2[N:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:16][CH:15]=2)[CH2:9]1)C1C=CC=CC=1.ClC(OC(Cl)C)=O.C(N(CC)C(C)C)(C)C>C1(C)C=CC=CC=1>[C:30]([O:29][C:27]([N:13]([C@@H:10]1[CH2:11][CH2:12][NH:8][CH2:9]1)[C:14]1[N:19]=[CH:18][C:17](/[CH:20]=[CH:21]/[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:16][CH:15]=1)=[O:28])([CH3:31])([CH3:32])[CH3:33]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5213051-Chloroethyl chloroformate2×HCID 86603618HCID 86603618, compound

Product 1

HCID 86603620HCID 86603620, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of ethyl (2E)-3-{6-[[(3R)-1-benzyl-3-pyrrolidinyl](tert-butoxycarbonyl)amino]-3-pyridyl}acrylate (5.45 g) in toluene (55 ml) was added 1-chloroethyl chloroformate (2.59 g) at room temperature and stirred at 20° C. for 1 hour. 1-Chloroethyl chloroformate (795 mg) and N,N-diisopropylethylamine (0.736 ml) was added to the mixture, and the solution was stirred at 20° C. for 15 minutes. After it was concentrated under reduced pressure, the resulting residue was dissolved in EtOH (70 ml). The mixture was stirred at 65° C. for 30 minutes, and concentrated under reduced pressure. The residue was poured into a mixture of aq NaHCO3 solution (80 ml) and dichloromethane (100 ml). The organic layer was separated and dried over sodium sulfate, and evaporated under reduced pressure to give crude oil. The oil was purified by column chromatography (silica gel 125 g, dichloromethane/MeOH (60/1 to 15/1) to give ethyl (2E)-3-(6-{(tert-butoxycarbonyl)[(3R)-3-pyrrolidinyl]amino}-3-pyridyl)acrylate as oil (2.0 g).

Workup

  1. stirringthe solution was stirred at 20° C. for 15 minutes
  2. concentrationAfter it was concentrated under reduced pressure
  3. dissolutionthe resulting residue was dissolved in EtOH (70 ml)
  4. stirringThe mixture was stirred at 65° C. for 30 minutes
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was poured into a mixture of aq NaHCO3 solution (80 ml) and dichloromethane (100 ml)
  7. customThe organic layer was separated
  8. dry with materialdried over sodium sulfate
  9. customevaporated under reduced pressure
  10. customto give crude oil
  11. customThe oil was purified by column chromatography (silica gel 125 g, dichloromethane/MeOH (60/1 to 15/1)

Sources & evidence

ORD record
ord-5223325d8617412dbcea59ae687f1650
Source dataset
uspto-grants-2009_07
Patent number
US07557127B2

Reaction notes

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