Hydrochloric Acid → HCID 69748516, compound

HRID 497469Notes

Reaction equation

HRID 497469 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[C@H:10]([C:15]([N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:18]2)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.C(=O)(O)[O-].[Na+]>B.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([NH2:14])[C@H:10]([CH2:15][N:17]2[CH2:22][CH2:21][CH2:20][C@@H:19]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:18]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 69748878HCID 69748878, compound

Product 1

HCID 69748516HCID 69748516, compoundYield 77%

Reagents, catalysts & solvents 2

HCID 6331BoraneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a dry flask (3R,4R)-4-amino-3-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester (500 mg, 1.19 mmol) was dissolved in borane (50 mL of a 1M solution in tetrahydrofuran, 50 mmol). The reaction was stirred 19 hours. The reaction was poured into hydrochloric acid (70 mL of a 1M aqueous solution) and stirred vigorously for 4 hours. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate. The layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, dried with magnesium sulfate, filtered and concentrated in vacuo. The mixture was purified by flash chromatography using 5-20% methanol in chloroform to give a yellow solid (371 mg, 77%). 1H NMR (300 MHz, CDCl3), δ: 7.08 (m, 2H), 6.97 (t, 2H, J=8), 4.08 (bs, 2H), 3.70 (bs, 1H), 3.34 (bs, 1H), 3.02 (bt, 1H, J=9), 2.68 (bm, 2H), 2.32 (bm, 7H), 1.98 (m, 1H), 1.75 (m, 5H), 1.44 (s, 9H), 0.89 (m, 1H).

Workup

  1. stirringstirred vigorously for 4 hours
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-5f932eee8f8c44e190aec751172e356d
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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