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

HRID 2079413Notes

Reaction equation

HRID 2079413 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 (101 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-7822bf64be424a28ba88f06129208dbe
Source dataset
uspto-grants-2011_04
Patent number
US07928107B2

Reaction notes

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