Potassium sodium tartarate → Tert-butyl 4-(6-{2-[2-fluoro-4-(hydroxymethyl)phenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylate

HRID 1465487Notes

Reaction equation

HRID 1465487 reaction equation
C([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][C:14]2[N:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)=[C:8]([F:33])[CH:7]=1)=O)C.O1CCCC1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>O1CCCC1>[F:33][C:8]1[CH:7]=[C:6]([CH2:4][OH:3])[CH:11]=[CH:10][C:9]=1[CH2:12][CH2:13][C:14]1[N:19]=[CH:18][C:17]([N:20]2[CH2:21][CH2:22][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:24][CH2:25]2)=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 9855836Potassium sodium tartarateHCID 58181293Tert-butyl 4-(6-{2-[4-(ethoxycarbonyl)-2-fluorophenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylateHCID 86597605diisobutylaluminium hydride THF2×

Product 1

HCID 58181298Tert-butyl 4-(6-{2-[2-fluoro-4-(hydroxymethyl)phenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylateYield 81.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of tert-butyl 4-(6-{2-[4-(ethoxycarbonyl)-2-fluorophenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylate (1.414 g, 3.091 mmol) in anhydrous tetrahydrofuran (15 ml) was added dropwise at −78° C. 1M diisobutylaluminum hydride tetrahydrofuran solution (12 ml, 12 mmol) over 10 mins. After stirring at −78° C. for 30 mins, the mixture was heated to room temperature and stirred for 1 hr 40 mins. After cooling to −78° C., 1M diisobutylaluminum hydride tetrahydrofuran solution (6 ml, 6 mmol) was added dropwise over 5 mins. The mixture was heated to room temperature and stirred for 40 mins. Saturated aqueous potassium sodium tartrate solution (150 ml) was added and the mixture was stirred and extracted 3 times with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=4:1→ethyl acetate) to give tert-butyl 4-(6-{2-[2-fluoro-4-(hydroxymethyl)phenyl]ethyl}pyridin-3-yl)piperazine-1-carboxylate (1.046 g, yield 81.4%) as a slightly yellow solid.

Workup

  1. temperaturethe mixture was heated to room temperature
  2. stirringstirred for 1 hr 40 mins
  3. temperatureAfter cooling to −78° C.
  4. temperatureThe mixture was heated to room temperature
  5. stirringstirred for 40 mins
  6. stirringthe mixture was stirred
  7. extractionextracted 3 times with ethyl acetate
  8. washThe combined organic layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=4:1→ethyl acetate)

Sources & evidence

ORD record
ord-b906eb18b20a4e23b23d6c2a91544e03
Source dataset
uspto-grants-2015_04
Patent number
US08999989B2

Reaction notes

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