Hydrogen Bromide → (R)-5-ethyl-5-hydroxy-2,5,6,9-tetrahydro-8-oxa-2-aza-benzocycloheptene

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Reaction Conditions

Reaction Steps

To a stirred solution of 3.00 g (R)-3-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-3-hydroxy-pentanoic acid (8.69 mmol), as obtainable from Example 10, in 11 mL 1,2-dimethoxyethane, were added 2.01 mL aqueous HBr (48%) (17.89 mmol, 2.06 eq). After 15 min at room temperature, the solution was heated to 50° C. After 4 h, the first product crystals appeared. The reaction was monitored by HPLC. After 24 h at 50° C. (<1% area (R)-3-(3-benzyloxymethyl-2-methoxy-pyridin-4-yl)-3-hydroxy-pentanoic acid), the reaction was cooled to room temperature. The mixture was allowed to stir at room temperature for 72 h and was then filtered. The solid was washed twice with 2.24 mL, in total with 4.48 mL TBME, and subsequently with 2.24 mL acetone; twice with 2.24 mL, in total with 4.48 mL water, and finally twice with 2.24 mL, in total with 4.48 mL acetone. After drying in vacuo, the title compound (1.040 g, 4.66 mmol, 54% by weight) was obtained as white crystals, and in an enantiomeric ratio of er=99.95:0.05 as determined by the following Chiral HPLC method:

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