Sodium hydride → HCID 178456443, compound

HRID 1931116Notes

Reaction equation

HRID 1931116 reaction equation
[H-].[Na+].[OH:3][CH2:4][C@H:5]1[NH:9][C:8](=[O:10])[CH2:7][CH2:6]1.[C:11]([C:15]1[N:19]([CH3:20])[N:18]([CH2:21][CH2:22][CH3:23])/[C:17](=[N:24]/[C:25](=[O:37])[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][C:27]=2F)/[CH:16]=1)([CH3:14])([CH3:13])[CH3:12]>CN(C)C=O>[C:11]([C:15]1[N:19]([CH3:20])[N:18]([CH2:21][CH2:22][CH3:23])/[C:17](=[N:24]/[C:25](=[O:37])[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:33])[F:34])[CH:29]=[CH:28][C:27]=2[O:3][CH2:4][C@@H:5]2[CH2:6][CH2:7][C:8](=[O:10])[NH:9]2)/[CH:16]=1)([CH3:12])([CH3:13])[CH3:14]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 643511(S)-5-(Hydroxymethyl)-2-pyrrolidinoneHCID 178456441HCID 178456441, compound

Product 1

HCID 178456443HCID 178456443, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (50 mg, 60% dispersion in mineral oil, 1.25 mmol) was added to a solution of (S)-5-(hydroxymethyl)pyrrolidin-2-one (72 mg, 0.62 mmol) in dimethylformamide (0.5 mL). After 10 minutes a solution of Example 125A (0.12 g, 0.31 mmol) in dimethylformamide (1.0 mL) was added and the mixture stirred for 3 hours. The reaction mixture was partitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL). The organic extract was washed with water and brine, dried with MgSO4, filtered and concentrated. The residue was purified by chromatography (hexanes:EtOAc:MeOH:Et3N (4:4:1:0.2) to afford the title compound (50 mg, 0.10 mmol, 33% yield). 1H NMR (500 MHz, Pyridine-d5) δ ppm 0.76 (t, J=7.5 Hz, 3H), 1.16 (s, 9H), 1.57-1.64 (m, 2H), 1.64-1.69 (m, 1H), 1.95-2.03 (m, 1H), 2.27 (ddd, J=16.9, 9.7, 7.3 Hz, 1H), 2.37-2.45 (m, 1H), 3.71 (s, 3H), 3.88 (t, J=9.3 Hz, 1H), 4.05-4.12 (m, 1H), 4.31 (t, J=7.3 Hz, 2H), 4.38 (dd, J=9.6, 3.5 Hz, 1H), 7.17 (d, J=8.5 Hz, 1H), 7.43 (s, 1H), 7.64 (dd, J=8.5, 2.1 Hz, 1H), 8.53 (d, J=2.1 Hz, 1H), 9.25 (s, 1H); MS (ESI+) m/z 481.2 [M+H]−. Anal. calculated for C24H31F3N4O3: C, 59.99; H, 6.50; N, 11.66. Found: C, 59.81; H, 6.45; N, 11.52.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (15 mL) and saturated NaHCO3 (1 mL)
  2. extractionThe organic extract
  3. washwas washed with water and brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (hexanes:EtOAc:MeOH:Et3N (4:4:1:0.2)

Sources & evidence

ORD record
ord-cc59e87a68894cae8e2fbc14d92bb2dd
Source dataset
uspto-grants-2012_05
Patent number
US08188135B2

Reaction notes

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