Tetrahydrofuran → HCID 178456442, compound

HRID 1931115Notes

Reaction equation

HRID 1931115 reaction equation
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[Na+].[C:7]([C:11]1[N:15]([CH3:16])[N:14]([CH2:17][CH2:18][CH3:19])/[C:13](=[N:20]/[C:21](=[O:33])[C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=2F)/[CH:12]=1)([CH3:10])([CH3:9])[CH3:8].C1C[O:37]CC1>>[C:7]([C:11]1[N:15]([CH3:16])[N:14]([CH2:17][CH2:18][CH3:19])/[C:13](=[N:20]/[C:21](=[O:33])[C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=2[O:37][CH2:1][C:2]([OH:4])([CH3:5])[CH3:3])/[CH:12]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 23676156Sodium t-butoxideHCID 178456441HCID 178456441, compound

Product 1

HCID 178456442HCID 178456442, compoundYield 56%

Procedure

Sodium t-butoxide (0.15 g, 1.6 mmol) was added to a solution of Example 81D (70 mg, 0.78 mmol) in THF (1 mL). After 10 minutes, a solution of Example 125A (0.15 g, 0.4 mmol) in THF (1 mL) was added and the mixture stirred for 3 hours. The reaction was partitioned between dichloromethane with and saturated NaHCO3. The organic extract was washed with water and brine, dried with MgSO4, filtered, and concentrated. The residue was purified by chromatography (SiO2, hexane:EtOAc:MeOH:Et3N (8:8:1:0.2)) then recrystallized from EtOAc and hexanes to afford the title compound (0.1 g, 0.22 mmol, 56% yield). 1H NMR (300 MHz, Methanol-d4) δ ppm 0.94 (t, J=7.5 Hz, 3H), 1.27 (s, 6H), 1.46 (s, 9H), 1.70-1.82 (m, 2H), 3.96 (s, 5H), 4.26-4.33 (m, 2H), 6.77 (s, 1H), 7.18 (d, J=8.5 Hz, 1H), 7.61 (dd, J=8.5, 2.0 Hz, 1H), 7.77 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 456.1 (M+H)+.

Workup

  1. customThe reaction was partitioned between dichloromethane with and saturated NaHCO3
  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 (SiO2, hexane:EtOAc:MeOH:Et3N (8:8:1:0.2))
  8. customthen recrystallized from EtOAc and hexanes

Sources & evidence

ORD record
ord-dc79c244b4174226a5487fcc807db07a
Source dataset
uspto-grants-2012_05
Patent number
US08188135B2

Reaction notes

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