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

HRID 646616Notes

Reaction equation

C(O[CH2:9][C:10]1[C:11](OC)=[N:12][CH:13]=[CH:14][C:15]=1[C@@:16]([OH:23])([CH2:21][CH3:22])[CH2:17][C:18](O)=[O:19])C1C=CC=CC=1.Br>COCCOC>[CH2:21]([C@:16]1([OH:23])[C:15]2[CH:14]=[CH:13][NH:12][CH2:11][C:10]=2[CH2:9][O:19][CH2:18][CH2:17]1)[CH3:22]

Participants

Conditions

Temperature: 50 °C

Procedure

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:

Workup

waitAfter 4 h
temperaturethe reaction was cooled to room temperature
filtrationwas then filtered
washThe solid was washed twice with 2.24 mL
customAfter drying in vacuo

Sources & evidence

ORD record: ord-a40753b66edd47e5bfd30049a2cc488c
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07705155B2

Reaction notes

Loading…