Sodium hydride → HCID 178456443, compound

HRID 536753Notes

Reaction equation

HRID 536753 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-ce0bf8fe0bef472a9d6a0de9bd315b4e
Source dataset
uspto-grants-2014_10
Patent number
US08859596B2

Reaction notes

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