Sodium hydride → Ammonium Acetate

HRID 1470042Notes

Reaction equation

HRID 1470042 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[S:13][C:12]([NH:14][C:15]([C:17]23[CH2:26][CH:21]4[CH2:22][CH:23]([CH2:25][CH:19]([CH2:20]4)[CH2:18]2)[CH2:24]3)=[O:16])=[N:11][CH:10]=1.Br[CH2:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][O:30]1.[H-].[Na+]>O1CCCC1.CN(C)C=O.O>[C:15]([O-:30])(=[O:16])[CH3:17].[NH4+:11].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[S:13]/[C:12](=[N:14]\[C:15]([C:17]23[CH2:26][CH:21]4[CH2:20][CH:19]([CH2:25][CH:23]([CH2:22]4)[CH2:24]2)[CH2:18]3)=[O:16])/[N:11]([CH2:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[CH:10]=1

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 87181398HCID 87181398, compound

Product 2

HCID 517165Ammonium AcetateHCID 178522741HCID 178522741, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A mixture of Example 200C (120 mg, 0.32 mmol), 2-(bromomethyl)tetrahydro-2H-pyran (62 mg, 0.35 mmol) and sodium hydride (60% dispersion in oil) (16 mg, 0.38 mmol) in tetrahydrofuran/N,N-dimethylformamide (2:1) (1 mL) was heated at 150° C. in a microwave (Emrys Personal Chemistry) for 30 minutes. The mixture was diluted with water, and extracted with ethyl acetate. The organic extract was dried (Na2SO4), filtered and concentrated. Purification by preparative high pressure liquid chromotography on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile: ammonium acetate (10 mM) over 15 minutes at a flow rate of 70 mL/minutes afforded the title compound. 1H NMR (400 MHz, dimethylsulfoxide-d6) δ ppm 1.17-1.30 (m, 1H) 1.40-1.51 (m, 3H) 1.60 (d, J=13.50 Hz, 1H) 1.64-1.76 (m, 7H) 1.76-1.83 (m, 1H) 1.85-1.89 (m, 6H) 1.96-2.03 (m, 3H) 3.74-3.83 (m, 1H) 3.88 (d, J=11.66 Hz, 1H) 4.18-4.28 (m, 2H) 7.20 (td, J=7.98, 2.76, 2.15 Hz, 1H) 7.38-7.45 (m, 1H) 7.66 (td, J=6.14 Hz, 1H) 7.80 (s, 1H); MS (ESI) m/z 473 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by preparative high pressure liquid chromotography on a Waters Symmetry C8 column (40 mm×100 mm, 7 μm particle size)

Sources & evidence

ORD record
ord-ed31ee671c4f412182f637bc2a2673f6
Source dataset
uspto-grants-2015_04
Patent number
US09006275B2

Reaction notes

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