Borane;tetrahydrofuran → HCID 44194573, compound

HRID 1192927Notes

Reaction equation

HRID 1192927 reaction equation
[CH2:1]([C@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[CH2:9][CH2:8][N:7]([C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH:19]=[CH:20][C:21](=[O:25])[N:22]([CH3:24])[CH:23]=3)=[CH:14][CH:13]=2)[CH3:11])[C:6](=[O:26])[CH2:5]1)[CH:2]=[CH2:3].B.C1C[O:38]CC1>C1COCC1>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C@@:4]2([CH2:1][CH2:2][CH2:3][OH:38])[CH2:9][CH2:8][N:7]([C@H:10]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:19]=[CH:20][C:21](=[O:25])[N:22]([CH3:24])[CH:23]=4)=[CH:14][CH:13]=3)[CH3:11])[C:6](=[O:26])[CH2:5]2)=[CH:28][CH:29]=1

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 58237948HCID 58237948, compound

Product 1

HCID 44194573HCID 44194573, compoundYield 2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(4-((S)-1-((S)-4-allyl-4-(4-fluorophenyl)-2-oxopiperidin-1-yl)ethyl)phenyl)-1-methylpyridin-2(1H)-one (45 mg, 0.10 mmol) in THF (3 mL) was added BH3/THF (0.3 mL, 1 M) at 0° C. under nitrogen atmosphere. The mixture was stirred for 2 h. The reaction was quenched with water. Aqueous NaOH solution (1 M, 0.6 mL) and H2O2 (0.3 mL□30%) were added to the above mixture. The resulting mixture was stirred for 1 h. The mixture was extracted with EtOAc and the combined organic phase was concentrated to give the crude product, which was purified by preparative HPLC to give 5-(4-((S)-1-((S)-4-(4-fluorophenyl)-4-(3-hydroxypropyl)-2-oxopiperidin-1-yl)ethyl)phenyl)-1-methylpyridin-2(1H)-one (1.0 mg, 2%). LC-MS Method 2, tR=1.63 min, m/z=463.1. 1H NMR (CDCl3): δ1.42 (t, 3H), 1.69 (m, 2H), 1.92 (m, 1H), 2.01 (m, 1H), 2.22 (m, 2H), 2.44 (d, 2H), 2.99 (m, 3H), 3.36 (m, 1H), 3.42 (t, 2H), 3.59 (s, 3H), 3.60 (m, 1H), 3.84 (m, 1H), 6.01 (q, 1H), 6.61 (d, 1H) □ 6.89 (m, 4H), 7.14 (m, 4H), 7.33 (d, 1H), 7.49 (m, 1H).

Workup

  1. customThe reaction was quenched with water
  2. additionAqueous NaOH solution (1 M, 0.6 mL) and H2O2 (0.3 mL□30%) were added to the above mixture
  3. stirringThe resulting mixture was stirred for 1 h
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationthe combined organic phase was concentrated
  6. customto give the crude product, which
  7. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-bfcee65657b44004b1ba120d8123be89
Source dataset
uspto-grants-2014_03
Patent number
US08680281B2

Reaction notes

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