Methanol → Racemic methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate

HRID 2402379Notes

Reaction equation

HRID 2402379 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[O:6]=[C:7]1[CH2:16][CH2:15][CH2:14][C:13]2[C:12]([C:17]([O:19][CH3:20])=[O:18])=[CH:11][CH:10]=[CH:9][C:8]1=2.CO>C1COCC1>[OH:6][C:7]1([C:2]2[S:1][CH:5]=[CH:4][N:3]=2)[CH2:16][CH2:15][CH2:14][C:13]2[C:12]([C:17]([O:19][CH3:20])=[O:18])=[CH:11][CH:10]=[CH:9][C:8]1=2

Participants

5

Reactant 3

HCID 887MethanolHCID 9256ThiazoleHCID 12284900Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylate

Product 1

HCID 70977660Racemic methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To an oven-dried, N2-purged flask was added isopropyl magnesium chloride lithium chloride complex (7.91 mL, 10.3 mmol) and THF (18.4 mL) and the solution was cooled to 0° C. A solution of thiazole (0.813 g, 9.55 mmol) in THF (9.18 mL) was then added, and the reaction was stirred for 45 min at 0° C., and then cooled to −10° C. A solution of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-1-carboxylate (1.5 g, 7.34 mmol) in THF (9.18 mL) was then added, after which the reaction was allowed to warm to rt over a period of 4 h. MeOH (5 mL) was then added and the reaction was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×50 mL), then the combined organic phases were dried (MgSO4), filtered and concentrated. The product was purified by silica gel chromatography using a gradient solvent system of 0-70% EtOAc/DCM. The product-containing fractions were collected and concentrated to give racemic methyl 5-hydroxy-5-(thiazol-2-yl)-5,6,7,8-tetrahydronaphthalene-1-carboxylate as a yellow oil. The enantiomers were resolved by chiral SFC using a Chiral Technology AY-H 2.1×25 cm, 5 uM column, eluting with 20%-50% MeOH+0.25% dimethyl ethylamine/CO2. At a flow rate of 70 mL/min, the two enantiomers eluted at 2.38 min and 2.79 min.

Workup

  1. customTo an oven-dried, N2-purged flask
  2. temperaturecooled to −10° C
  3. temperatureto warm to rt over a period of 4 h
  4. customthe reaction was partitioned between water (50 mL) and EtOAc (50 mL)
  5. extractionThe aqueous phase was extracted with EtOAc (2×50 mL)
  6. dry with materialthe combined organic phases were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by silica gel chromatography
  10. customThe product-containing fractions were collected
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-ce1c58a022a44b6386c0e6fcc35db89b
Source dataset
uspto-grants-2014_08
Patent number
US08796310B2

Reaction notes

Loading…