HCID 69751452, compound → HCID 69751784, compound

HRID 497471Notes

Reaction equation

HRID 497471 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]([N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:17]2)=O)[C@@H:10]([NH:30]C(NC2C=CC=C(C(=O)C)C=2)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>B.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([CH2:14][N:16]2[CH2:21][CH2:20][CH2:19][C@@H:18]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:17]2)[C@@H:10]([NH2:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 1

HCID 69751452HCID 69751452, compound

Product 1

HCID 69751784HCID 69751784, compoundYield 22.5%

Reagents, catalysts & solvents 2

HCID 6331BoraneSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a dry flask (3R,4R)-3-[3-(3-acetyl-phenyl)-ureido]-4-[(S)-3-(4-fluoro-benzyl)-piperidine-1-carbonyl]-piperidine-1-carboxylic acid t-butyl ester (1.19 g, 2.84 mmol) was dissolved in borane (100 mL of a 1M solution in tetrahydrofuran, 100 mmol). The reaction was stirred 19 hours. The reaction mixture was concentrated in vacuo and redissolved in 800 mL of ethyl acetate. The solution was poured into hydrochloric acid (140 mL of a 1M aqueous solution) and stirred vigorously for 16 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 20-0% hexane/ethyl acetate to give a light yellow solid (0.259 g, 22%). 1H NMR (300 MHz, CD3OD), δ: 7.18 (m, 2H), 7.04 (m, 2H), 4.37 (m, 2H), 4.19 (m, 2H), 3.47 (m, 1H), 3.20 (m, 1H), 2.89 (m, 1H), 2.68 (m, 2H), 2.52 (m, 4H), 1.88 (m, 2H), 1.75 (m, 2H), 1.55 (m, 2H), 1.45 (m, 2H), 1.44 (s, 9H). MS (ESI), m+/z: (M+H)+=406.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionredissolved in 800 mL of ethyl acetate
  3. additionThe solution was poured into hydrochloric acid (140 mL of a 1M aqueous solution) and
  4. stirringstirred vigorously for 16 hours
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate
  7. dry with materialdried with magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe mixture was purified by flash chromatography

Sources & evidence

ORD record
ord-20f06bfb18254179813b8640d512d75a
Source dataset
uspto-grants-2005_09
Patent number
US06949546B2

Reaction notes

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