Triethylamine → 1,1-Dimethylethyl (3R)-3-[(cyclopropylcarbonyl)amino]-1-pyrrolidinecarboxylate

HRID 2062329Notes

Reaction equation

HRID 2062329 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]1.[CH:14]1([C:17](O)=[O:18])[CH2:16][CH2:15]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl>[CH:14]1([C:17]([NH:1][C@@H:2]2[CH2:6][CH2:5][N:4]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:3]2)=[O:18])[CH2:16][CH2:15]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 15655Cyclopropanecarboxylic acidHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 586838971,1-Dimethylethyl (3R)-3-[(cyclopropylcarbonyl)amino]-1-pyrrolidinecarboxylateYield 73.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of (R)-tert-butyl 3-aminopyrrolidine-1-carboxylate (500 mg, 2.68 mmol) in CH2Cl2 (10 mL) was added cyclopropanecarboxylic acid (276 μL, 3.48 mmol), followed by the addition of HATU (1.3 g, 3.48 mmol) and triethylamine (725 μL, 5.2 mmol). The reaction was complete after stirring for 1 h. After quenching with water, the aqueous layer was extracted twice with CH2Cl2, and the combined organic extracts were dried over MgSO4, filtered, and concentrated. The crude material was purified via silica gel chromatography 0-20% EtOAc/CH2Cl2 to afford (R)-tert-butyl 3-(cyclopropanecarboxamido)pyrrolidine-1-carboxylate (500 mg, 73%). LC/MS: m/z 255.3 (M+H)+ at 2.33 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Workup

  1. customAfter quenching with water
  2. extractionthe aqueous layer was extracted twice with CH2Cl2
  3. dry with materialthe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified via silica gel chromatography 0-20% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-257e7b4bee80427ba3aacd49326ede7d
Source dataset
uspto-grants-2012_10
Patent number
US08283354B2

Reaction notes

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