Sodium borohydride → HCID 131723272, compound

HRID 2186356Notes

Reaction equation

HRID 2186356 reaction equation
[BH4-].[Na+].[O:3]=[C:4]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][CH:26]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]#[C:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][C@@H:8]1[C:21]([O:23][CH3:24])=[O:22]>CO.O>[OH:3][CH:4]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([O:35][CH3:36])[CH:33]=2)[N:28]=[CH:27][CH:26]=1)[CH2:5][CH2:6][C@@H:7]1[CH2:12][CH2:11][N:10]([CH2:13][C:14]#[C:15][C:16]2[S:17][CH:18]=[CH:19][CH:20]=2)[CH2:9][C@@H:8]1[C:21]([O:23][CH3:24])=[O:22]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 131723273HCID 131723273, compound

Product 1

HCID 131723272HCID 131723272, compoundYield 80.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

0.15 g of sodium borohydride was added in one portion, at a temperature in the region of 20° C. and under an inert atmosphere, to a stirred solution of 1.6 g of methyl (3R,4R)-4-[3-oxo-3-(6-methoxyquinolin-4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]-piperidine-3-carboxylate in 15 cm3 of methanol. The mixture was subsequently stirred for 2.5 hours at a temperature in the region of 25° C. 15 cm3 of distilled water were then added dropwise over approximately 10 minutes while maintaining at a temperature in the region of 15° C. The mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The residue obtained was taken up in 20 cm3 of distilled water. The mixture was extracted with a total of 100 cm3 of dichloromethane. The organic phases were combined, dried over sodium sulfate, and then evaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C. The solid obtained was purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 20-45 μm; diameter 3 cm; height 35 cm), elution was carried out with a mixture of ethyl acetate and cyclohexane (8/2 by volume), and 15-cm3 fractions were collected. Fractions 38 to 59 were combined and then evaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C. 1.3 g of methyl (3R,4R)-4-[3-(R,S)-hydroxy-3-(6-methoxyquinolin4-yl)propyl]-1-[3-(thien-2-yl)prop-2-ynyl]piperidine-3-carboxylate were thus obtained in the form of a foam.

Workup

  1. temperaturewhile maintaining at a temperature in the region of 15° C
  2. concentrationThe mixture was concentrated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  3. customThe residue obtained
  4. extractionThe mixture was extracted with a total of 100 cm3 of dichloromethane
  5. dry with materialdried over sodium sulfate
  6. customevaporated under reduced pressure (5 kPa) at a temperature in the region of 40° C
  7. customThe solid obtained
  8. customwas purified by chromatography under argon pressure (50 kPa)
  9. washon a column of silica gel (particle size 20-45 μm; diameter 3 cm; height 35 cm), elution
  10. additionwas carried out with a mixture of ethyl acetate and cyclohexane (8/2 by volume), and 15-cm3 fractions
  11. customwere collected
  12. customevaporated under reduced pressure (2 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-4239d57240bc40c580cc3d39696f9f16
Source dataset
uspto-grants-2002_06
Patent number
US06403610B1

Reaction notes

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