1,2-Dichloroethane → (R)-2-(2-benzyloxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2215959Notes

Reaction equation

HRID 2215959 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:16]([CH:19]1[CH:23]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:22][C:21](=[O:32])[CH2:20]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>O1CCCC1.O.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@@H:9]1[C:13](=[O:15])[NH:16][CH:19]1[CH2:20][C:21](=[O:32])[O:22][CH:23]1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 11776TriphenylphosphineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 865885864-Azido-5-benzyloxy-dihydrofuran-2-one

Product 1

HCID 68575263(R)-2-(2-benzyloxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 49.4%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (S)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (0.13 g, 0.6 mmol), 4-azido-5-benzyloxy-dihydrofuran-2-one (0.14 g, 0.6 mmol) and triphenylphosphine (0.28 g, 1.0 mmol) in tetrahydrofuran (5 mL) and water (5 drops) was stirred under nitrogen for 0.5 h at room temperature and for 2 h at 65° C. The reaction was cooled to room temperature, was treated with with di-isopropylethylamine (0.52 mL, 5.0 mmol), EDC (0.15 g, 0.75 mmol), and HOBT (0.10 g, 0.75 mmol) and was stirred at room temperature under nitrogen for 20 h. 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 flash chromatography (SiO2) eluted with 2:3 ethyl acetate:hexanes provided (R)-2-(2-benzyloxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.12 g, 49% yield) as a sticky resin. 1H-NMR (500 MHz, CDCl3) δ 7.63 (br d, J=7.6 Hz, 0.7H), 7.28 (m, 5H), 6.50 (br, 0.3H), 5.37 (br s, 0.5H), 5.33 (s, 0.5H), 4.77 (d, J=11.6 Hz, 1H), 4.56 (dd, J=11.6, 3.7 Hz, 1H), 4.37 (br s, 1H), 4.18 (br s, 1H), 3.32 (br s, 1.4H), 3.24 (br s, 0.6H), 2.97 (br d, J=11.6 Hz, 1H), 2.35 (dd, J=18.1, 1.7 Hz, 1H), 2.1-2.3 (br, 1H), 1.81 (br s, 3H), 1.58 (s, 9H) ppm. MS (ES+): m/e=405 (M+H).

Workup

  1. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  2. dry with materialwas dried over sodium sulfate
  3. customwas evaporated
  4. customPurification by flash chromatography (SiO2)
  5. washeluted with 2:3 ethyl acetate

Sources & evidence

ORD record
ord-a0c26e1329254e27aecb3087303e4504
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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