4-Toluenesulfonyl chloride → HCID 14804600, compound

HRID 1586104Notes

Reaction equation

HRID 1586104 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[C@@H:5]1[CH2:9][C@H:8]([OH:10])[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[CH3:2].[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1>C(Cl)(Cl)Cl.C(Cl)Cl.N1C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:21])[C@@H:5]1[CH2:9][C@H:8]([O:10][S:28]([C:25]2[CH:26]=[CH:27][C:22]([CH3:32])=[CH:23][CH:24]=2)(=[O:30])=[O:29])[CH2:7][N:6]1[C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])[CH3:2]

Participants

6

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 183915071,2-Pyrrolidinedicarboxylic acid, 4-hydroxy-, 2-ethyl 1-(phenylmethyl) ester, (2S-cis)-

Product 1

HCID 14804600HCID 14804600, compoundYield 80%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolvent2×HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-CBZ-cis-4-hydroxy-L-proline ethyl ester (6.4 g, 22 mmol) and anhydrous pyridine (5.3 mL, 5.2 g, 65 mmol) in CHCl3 (35 mL) was added p-toluenesulfonyl chloride (8.3 g, 44 mmol) in one portion. After stirring at room temperature for 7 days, the reaction was diluted with CH2Cl2 (100 mL) and pyridine removed by extraction with 10% HCl (4×13 mL). The organic layer was dried (MgSO4) and concentrated to a yellow oil which was purified by flash chromatography (silica gel, using 5:4 petroleum ether-ether) affording 7.8 g (80%) of 5 as colorless needles: mp 91°-92° C.; TLC Rf 0.15 (4:2 ethyl ether-petroleum ether); [α25D -26° (c 1.1, CHCl3); 1H NMR (250 MHz, CDCl3) δ 7.75 (app d, J=8.4 Hz, 2 H), 7.34-7.28 (m, 7 H), 5.18-5.04 (m, 3 H, PhCH2 and H-4), 4.52-4.41 (m, 1 H, H-2), 4.20-4.02 (m, 2 H, CO2CH2CH3), 3.78-3.62 (m, 1 H, H-5), 2.48-2.37 (m, 2 H, H-3), 2.45+2.44 (s, 3 H, PhCH3, two rotamers), 1.22+1.14 (t, J=7.1 Hz, 3 H, CO2CH2CH3); 13C NMR (75.5 MHz, CDCl3) δ 170.89, 170.57, 154.20, 153.89, 145.12, 145.09, 136.11, 133.88, 129.91, 129.85, 128.38, 128.32, 128.03, 127.98, 127.86, 127.77, 127.58, 78.62, 77.74, 67.21, 67.15, 61.47, 57.53, 57.30, 52.25, 51.99, 37.07, 35.98, 21.59, 13.92, 13.85; IR (CHCl3) 2995, 1745, 1700, 1415, 1360, 1175, 1120, 1050, 1020 cm1. Anal. Calcd for C22H25NO7S: C, 59.05; H, 5.63; N, 3.13. Found: C, 59.08; H, 5.54; N, 3.11.

Workup

  1. customremoved by extraction with 10% HCl (4×13 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated to a yellow oil which
  4. customwas purified by flash chromatography (silica gel, using 5:4 petroleum ether-ether)

Sources & evidence

ORD record
ord-ca44fa71075d40169e4d6f02edd64f87
Source dataset
uspto-grants-1999_08
Patent number
US05942537

Reaction notes

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