2-Acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acid → 2-(2-Hydroxypropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid

HRID 1690796Notes

Reaction equation

HRID 1690796 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][C:11]2[CH2:10][CH:9]([C:14]([OH:16])=[O:15])[CH2:8][CH2:7][C:6]=2[N:5]=1)(=[O:3])[CH3:2].[CH3:17][Mg]Cl>C1COCC1>[OH:3][C:1]([C:4]1[CH:13]=[CH:12][C:11]2[CH2:10][CH:9]([C:14]([OH:16])=[O:15])[CH2:8][CH2:7][C:6]=2[N:5]=1)([CH3:17])[CH3:2]

Participants

4

Reactant 2

HCID 581186172-Acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acidHCID 178418332HCID 178418332, compound

Product 1

HCID 581186092-(2-Hydroxypropan-2-yl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a 25 mL flask was added 2-acetyl-5,6,7,8-tetrahydroquinoline-6-carboxylic acid (146 mg, 0.667 mmol) and tetrahydrofuran (2.7 mL). The system was purged with nitrogen and cooled to 0° C. 3M of methylmagnesium chloride in tetrahydrofuran (0.598 mL, 2.00 mmol) was added dropwise over 3 minutes. The mixture was stirred at 0° C. for 5 minutes then allowed to warm to room temperature. Additional THF (5 mL) was added and the mixture was sonicated for 1 minute to break up solids. After a total of 2 hours the reaction was carefully quenched by dropwise addition of 1M NaH2PO4 (10 mL). The mixture was diluted with DCM (10 mL) and citric acid (0.5 mL) was added to obtain a pH of 4. The layers were separated and the aqueous was extracted with 3:1 DCM/THF (10 mL) followed by with 3:1 CHCl3/IPA (15 mL×2), dried (Na2SO4), filtered and evaporated to obtain a reddish foam (160 mg, theoretical yield), which was used directly in the next step. m/z=236.2 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 7.55 (d, J=8.1 Hz, 1H), 7.39 (d, J=8.1 Hz, 1H), 3.10-2.90 (m, 4H), 2.85-2.74 (m, 1H), 2.32-2.25 (m, 1H), 2.06-1.95 (m, 1H), 1.51 (s, 6H).

Workup

  1. customThe system was purged with nitrogen
  2. temperatureto warm to room temperature
  3. customthe mixture was sonicated for 1 minute
  4. customAfter a total of 2 hours the reaction was carefully quenched by dropwise addition of 1M NaH2PO4 (10 mL)
  5. additionThe mixture was diluted with DCM (10 mL) and citric acid (0.5 mL)
  6. additionwas added
  7. customto obtain a pH of 4
  8. customThe layers were separated
  9. extractionthe aqueous was extracted with 3:1 DCM/THF (10 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. customevaporated
  13. customto obtain
  14. customa reddish foam (160 mg, theoretical yield), which

Sources & evidence

ORD record
ord-04c599b245ef46288239c29a9ce68681
Source dataset
uspto-grants-2012_04
Patent number
US08153651B2

Reaction notes

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