HCID 86633500, compound → HCID 86633502, compound

HRID 1255224Notes

Reaction equation

HRID 1255224 reaction equation
[Li][CH2:2]CCC.[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:42])([F:41])[O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[N:26]=[C:25]([N:27]3[C:31]([C:32]([F:35])([F:34])[F:33])=[C:30]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:29]=[N:28]3)[CH:24]=[CH:23][CH:22]=2)=[C:9]([CH:43]=O)[CH:8]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[Br:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([F:41])([F:42])[O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[C:21]2[N:26]=[C:25]([N:27]3[C:31]([C:32]([F:33])([F:35])[F:34])=[C:30]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:29]=[N:28]3)[CH:24]=[CH:23][CH:22]=2)=[C:9]([CH:43]=[CH2:2])[CH:8]=1

Participants

5

Reactant 2

HCID 86633500HCID 86633500, compoundHCID 178418339Butyllithium

Product 1

HCID 86633502HCID 86633502, compound

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (0° C.) suspension of methyltriphenyl phosphonium bromide (5.33 g, 14.9 mmol) in THF (100 mL) was added dropwise n-BuLi (5.5 mL, 2.5 M in hexanes, 13.8 mmol). After aging for 40 min, the reaction mixture was allowed to warm up to ambient temperature for 25 min, at which point 7.4 mL of the supernatant was taken and added to the title compound from Example 302 Step D (270 mg, 0.442 mmol). After 30 min, the mixture was quenched by addition of water and the aqueous phase was extracted with hexane-EtOAc. The organic phase was separated and concentrated in vacuo. Purification by silica gel flash chromatography (5% to 15% EtOAc in hexanes) provided the title compound: LCMS m/z 590.5 [M−F]+; 1H NMR (500 MHz, CD2Cl2) δ 8.13 (s, 1H), 7.86 (m, 2H), 7.77 (m, 2H), 7.60 (d, J=8.0 Hz, 1H), 7.55-7.48 (m, 2H), 7.45-7.40 (m, 3H), 7.08 (m, 1H), 5.68 (d, J=17.2 Hz, 1H), 5.32 (d, J=11.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 1.40 (t, J=7.2 Hz, 3H).

Workup

  1. temperatureTo a cooled
  2. waitAfter 30 min
  3. customthe mixture was quenched by addition of water
  4. extractionthe aqueous phase was extracted with hexane-EtOAc
  5. customThe organic phase was separated
  6. concentrationconcentrated in vacuo
  7. customPurification by silica gel flash chromatography (5% to 15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-1b076edd78be44d3ab5691213f65411b
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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