Triethylamine → 5-Hydroxymethyl-1,3-dihydro-isoindole-2-carboxylic acid benzyl ester

A mixture of (2,3-dihydro-1H-isoindol-5-yl)-methanol (1.34 g, 9.0 mmol) in anhydrous tetrahydrofuran (50 ml) was warmed gently to aid dissolution and allowed to cool to room temperature. Triethylamine (1.5 ml, 10.8 mmol) was added and the stirred mixture was treated dropwise with benzyl chloroformate (1.35 ml, 9.5 mmol) and stirred at room temperature for 3 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (30 ml) and 2M hydrochloric acid (30 ml). The organic layer was washed with water (30 ml), separated and the solvent removed in vacuo to afford a pink oil that solidified upon standing. The solids were triturated with 10% ethyl acetate in hexane (10 ml), filtered, rinsed with heptane (10 ml) and sucked dry to afford the title compound (2.5 g, 98%) as a pale pink solid. 1H NMR (DMSO-d6) 7.45-7.21 (8H, m), 5.20 (1H, t), 5.17 (2H, s), 4.71 (2H, br s), 4.64 (2H, br s), 4.50 (2H, d). MS: [M+H]+ 284.

1. temperaturewas warmed gently
2. dissolutiondissolution
3. customThe solvent was removed in vacuo
4. customthe residue partitioned between ethyl acetate (30 ml) and 2M hydrochloric acid (30 ml)
5. washThe organic layer was washed with water (30 ml)
6. customseparated
7. customthe solvent removed in vacuo
8. customto afford a pink oil
9. customThe solids were triturated with 10% ethyl acetate in hexane (10 ml)
10. filtrationfiltered
11. washrinsed with heptane (10 ml)
12. customsucked dry

ORD record

ord-19aa564a4d4941799eba1a67274cb221

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653084B2