p-Toluenesulfonic acid monohydrate → HCID 57535334, compound

HRID 1455571Notes

Reaction equation

HRID 1455571 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH:4]([NH:19][C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[CH2:5][C:6](=[O:18])[CH:7]([CH:15]([CH3:17])[CH3:16])C(OC(C)(C)C)=O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:30])[C@@H:4]([NH:19][C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])[CH2:5][C:6](=[O:18])[CH2:7][CH:15]([CH3:17])[CH3:16]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 68824693HCID 68824693, compound

Product 1

HCID 57535334HCID 57535334, compoundYield 90.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 5-Benzyloxycarbonylamino-2-isopropyl-3-oxo-hexanedioic acid 1-tert-butyl ester 6-methyl ester (1.06 g, 2.51 mmol) and p-toluenesulfonic acid monohydrate (35.8 mg, 0.19 mmol) in toluene (20 mL) is heated to reflux under N2 for 6.5 hr. The mixture is cooled to room temperature, and concentrated in vacuum. The residue is purified over 35 g silica gel, eluting with EtOAc:Heptane (1:4) to afford (S)-2-Benzyloxycarbonylamino-6-methyl-4-oxo-heptanoic acid methyl ester (727 mg, 90%). 1H NMR (CDCl3): δ 7.4 (m, 5H), 5.78 (d, J=9.1 Hz, 1H), 5.13 (s, 2H), 4.6 (m, 1H), 3.74 (s, 3H), 3.2 (dd, J=18.3, 4.4 Hz, 1H), 2.95 (dd, J=18.2, 4.0 Hz, 1H), 2.3 (m, 2H), 2.1 (m, 1H), 0.92 (d, J=6.7 Hz, 6H); LC/MS: 77% 322 (MH+).

Workup

  1. temperatureto reflux under N2 for 6.5 hr
  2. concentrationconcentrated in vacuum
  3. customThe residue is purified over 35 g silica gel
  4. washeluting with EtOAc:Heptane (1:4)

Sources & evidence

ORD record
ord-dcacdea5103742438c4e73d762981ad0
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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