Tetrahydro-4H-pyran-4-one → HCID 71622843, compound

HRID 1479070Notes

Reaction equation

HRID 1479070 reaction equation
C(O)=O.[Cl:4][C:5]1[C:13]([CH3:14])=[N:12][C:11]2[N:7]([N:8]=[C:9]3[CH2:17][N:16]([C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=4[O:27][C@H:28]4[CH2:32][CH2:31][NH:30][CH2:29]4)=[O:19])[CH2:15][C:10]3=2)[C:6]=1[CH3:33].[O:34]1[CH2:39][CH2:38][C:37](=O)[CH2:36][CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C(Cl)Cl>[Cl:4][C:5]1[C:13]([CH3:14])=[N:12][C:11]2[N:7]([N:8]=[C:9]3[CH2:17][N:16]([C:18]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=4[O:27][C@H:28]4[CH2:32][CH2:31][N:30]([CH:37]5[CH2:38][CH2:39][O:34][CH2:35][CH2:36]5)[CH2:29]4)=[O:19])[CH2:15][C:10]3=2)[C:6]=1[CH3:33]

Participants

6

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 5049666Sodium triacetoxyborohydrideHCID 131736546HCID 131736546, compound

Product 1

HCID 71622843HCID 71622843, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of Example 83 (150 mg; 0.35 mmol; 1 eq.), tetrahydropyran-4-one (52 mg; 0.52 mmol; 1.5 eq.) and sodium triacetoxyborohydride (74 mg; 0.35 mmol; 1 eq.) in DCE (4 mL) was stirred at 50° C. for 16 hours. The reaction mixture was diluted with DCM, washed with sat. aq. NaHCO3, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (EA to EA/MeOH/TEA, 90/10/2) afforded the title compound (100 mg, 56%) as white foam. 1H NMR (DMSO-d6) δ 7.41-7.30 (m, 1H), 6.99 (dd, J=11.5, 2.2 Hz, 1H), 6.87 (td, J=8.4, 2.3 Hz, 1H), 5.04-4.94 (m, 1H), 4.84-4.78 (m, 2H), 4.73-4.45 (m, 2H), 3.75-3.58 (m, 2H), 3.21-3.05 (m, 2H), 2.84 (s, 1.5H), 2.81 (s, 1.5H), 2.79-2.63 (m, 3H), 2.62 (s, 1.5H), 2.56 (s, 1.5H), 2.35-2.14 (m, 2H), 2.14-2.00 (m, 1H), 1.80-1.67 (m, 1H), 1.62-1.50 (m, 2H), 1.30-1.02 (m, 2H). HPLC (max plot) 94.2%, Rt 2.83 min. UPLC/MS: (MS+) 514.6 ([M+H]+).

Workup

  1. washwashed with sat. aq. NaHCO3
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by column chromatography (EA to EA/MeOH/TEA, 90/10/2)

Sources & evidence

ORD record
ord-5cf2cc3a1fcf41c391680d5124e0c905
Source dataset
uspto-grants-2016_08
Patent number
US09403835B2

Reaction notes

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