Methylparaben → methyl 4-[trans-1-tert-butoxycarbonyl-4-dimethylamino(2S)-pyrrolidinyl]methoxybenzoate

HRID 350517Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([N:13]([CH3:15])[CH3:14])[CH2:10][C@H:9]1[CH2:16][OH:17])=[O:7])([CH3:4])([CH3:3])[CH3:2].O[C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([N:13]([CH3:14])[CH3:15])[CH2:10][C@H:9]1[CH2:16][O:17][C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

To a stirred solution of trans-1-tert-butoxycarbonyl-4-dimethylamino-(2S)-hydroxymethyl pyrrolidine (180 mg, 0.73 mmol), methyl 4-hydroxybenzoate (114 mg, 0.75 mmol), and Ph3P (296 mg, 1.13 mmol) in THF (10 ml) was added DIAD (227 mg, 1.13 mmol) at 0° C. The reaction mixture was stirred at 70° C. for 18 hr. The mixture was concentrated in vacuo. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:2, v/v) to MeOH—CH2Cl2(5:95, v/v) as eluent to give methyl 4-[trans-1-tert-butoxycarbonyl-4-dimethylamino-(2S)-pyrrolidinyl]methoxybenzoate (180 mg, 68%) as a pale yellow oil. 1H-NMR (CDCl3) δ 1.46 (s, 9H), 1.80–1.95 (m, 1H), 2.20–2.23 (m, 1H), 2.24 (s, 6H), 2.90–2.95 (m, 1H), 3.10–3.30 (m, 1H), 3.50–3.65 (m, 1H), 3.88 (s, 3H), 3.95–4.35 (m, 3H), 6.93–6.95 (m, 2H), 7.96–7.98 (m, 2H).

Workup

concentrationThe mixture was concentrated in vacuo
customThe residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:2

Sources & evidence

ORD record: ord-2af06c549a7b47c5ab324bbbb4619919
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07179819B2

Reaction notes

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