6-Methoxy-alpha-tetralone → HCID 18434415, compound

HRID 1532778Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH2:9][CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[N:6][CH:7]=1.[Li]CCCC.[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[CH2:28][CH2:27][CH2:26]2.C([O-])(O)=O.[Na+]>C1COCC1>[CH3:21][O:22][C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29]([C:2]1[CH:7]=[N:6][C:5]([O:8][CH2:9][CH2:10][N:11]3[CH2:15][CH2:14][CH2:13][CH2:12]3)=[CH:4][CH:3]=1)([OH:33])[CH2:28][CH2:27][CH2:26]2

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 5-Bromo-2-(2-pyrrolidin-1-ylethoxy)pyridine (7.0 g, 26 mmol) in dry THF (50 mL) at −78° C. was added n-BuLi (2.5 M in hexanes, 12.4 mL, 31.0 mmol) dropwise. After 30 min, 6-methoxy-1-tetralone (4.55 g, 25.8 mmol) in dry THF was added. After stirring for 15 min at −78° C., the reaction was allowed to warm to room temperature. After 30 min, the reaction was poured into aq NaHCO3 (satd). The aqueous layer was extracted with EtOAc (2x). The combined organic solutions were dried (MgSO4), filtered, and concentrated. Flash chromatography (CHCl3: MeOH, 95:5) provided the alcohol (4.23 g, 44%) as a white solid. 1H NMR (250 MHz, CDCl3): δ8.07 (d, J=2.5 Hz, 1 H), 7.49 (dd, J=2.5, 8.7 Hz, 1 H), 7.00 (d, J=8.5 Hz, 1 H), 6.73 (m, 3 H), 4.45 (t, J=5.7 Hz, 2 H), 3.79 (s, 3 H), 2.92 (t, J=5.7 Hz, 2 H), 2.76 (m, 2 H), 2.67 (m, 4 H), 2.11 (s, 1 H), 2.08 (m, 3 H), 1.82 (m, 5 H).

Workup

temperatureto warm to room temperature
waitAfter 30 min
extractionThe aqueous layer was extracted with EtOAc (2x)
dry with materialThe combined organic solutions were dried (MgSO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-23fd68339f964aba9657ac825f7bbc7e
Source dataset: uspto-grants-2001_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06204286B1

Reaction notes

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