Diisopropylethylamine → (R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2215965Notes

Reaction equation

HRID 2215965 reaction equation
[NH2:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@H:19]1[C:23](O)=[O:24])=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>ClCCl.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](=[O:24])[NH:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 219532364-amino-5-ethoxy-5H-furan-2-one

Product 1

HCID 68576080(R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-amino-5-ethoxy-5H-furan-2-one (0.04 g, 0.30 mmol), (S)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.07 g, 0.30 mmol), diisopropylethylamine (0.12 mL, 0.66 mmol) and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (0.14 g, 0.38 mmol) in dichloromethane (3 mL) was stirred 24 h, was evaporated, was redissolved in 1-methyl-pyrrolidinone (3 mL) and was stirred 3 d. The reaction was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by two flash chromatographies (SiO2), eluted first with 4:6, then with 35:65 ethyl acetate:hexanes afforded (R )-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.009 g, 9% yield) as a film. 1H-NMR (500 MHz, CDCl3) δ 10.2 (br s, 0.7H), 10.1 (br s, 0.3H), 6.21 (br s, 0.7H), 6.17 (br s, 0.3H), 5.68 (s, 0.7H), 5.60 (br s, 0.3H), 4.38 (br s, 1H), 3.85 (m, 1H), 3.72 (m, 1H), 3.25-3.45 (m, 2H), 2.53 (br d, 12.5 Hz, 0.7H), 2.1 (br, 0.3H), 1.87 (br m, 3H), 1.44 (s, 9H), 1.21 (m, 3H) ppm. MS (ES+): m/e=341 (M+H).

Workup

  1. customwas evaporated
  2. dissolutionwas redissolved in 1-methyl-pyrrolidinone (3 mL)
  3. additionThe reaction was diluted with ethyl acetate
  4. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  5. dry with materialwas dried over sodium sulfate
  6. customwas evaporated
  7. customPurification by two flash chromatographies (SiO2)
  8. washeluted first with 4:6

Sources & evidence

ORD record
ord-ac75b6e2d5b543bc967845c0d62acaf3
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

Loading…