Methanol → HCID 178448629、化合物

HRID 1931101ノート

反応式

HRID 1931101 の反応式
[CH3:1][C:2]([CH3:5])([O-:4])[CH3:3].[K+].[CH2:7]([N:11]1[N:12]([CH3:34])[C:13]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:14]/[C:15]/1=[N:16]\[C:17](=[O:29])[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1F)[CH2:8][CH2:9][CH3:10].CC[O:37]C(C)=O.CO>C1COCC1.CCN(CC)CC>[CH2:7]([N:11]1[N:12]([CH3:34])[C:13]([C:30]([CH3:33])([CH3:32])[CH3:31])=[CH:14]/[C:15]/1=[N:16]\[C:17](=[O:29])[C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[O:37][CH2:1][C:2]([OH:4])([CH3:5])[CH3:3])[CH2:8][CH2:9][CH3:10]

参加物

7

反応物 4

HCID 887MethanolHCID 8857Ethyl Acetate2 回HCID 23665647Potassium tert-butoxideHCID 178448620HCID 178448620、化合物

生成物 1

HCID 178448629HCID 178448629、化合物収率 57%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8471Triethylamine溶媒

実験手順

To a solution of Example 81D (7.6 g, 84 mmol) in THF (300 mL) at 0° C. was added potassium tert-butoxide (18.9 g, 168 mmol). The ice bath was removed and the mixture was stirred for 45 min then a solution of Example 81C (22.4 g, 56.1 mmol) in THF (100 mL) was added. The mixture was stirred for 2 hours at ambient temperature then partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL). The layers were separated and the aqueous phase was extracted with EtOAc (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. Purification by column chromatography (SiO2, 50% hexanes/EtOAc then 100% EtOAc then 9:1:0.1 EtOAc:MeOH:Et3N) afforded the title compound (15 g, 31.9 mmol, 57% yield). 1H NMR (300 MHz, CDCl3) δ ppm 0.95 (t, J=7.3 Hz, 3H) 1.28 (s, 6H) 1.32-1.42 (m, 2H) 1.42 (s, 9H) 1.61-1.72 (m, 2H) 3.75 (s, 3H) 4.03 (s, 2H) 4.27 (dd, J=7.8 Hz, 2H) 6.16 (s, 1H) 7.00 (d, J=8.5 Hz, 1H) 6.99 (s, 1H) 7.51 (dd, J=8.6, 1.9 Hz, 1H) 8.13 (d, J=2.4 Hz, 1 H); MS (DCI/NH3) m/z 470 (M+H)+; Anal. calculated for C24H34F3N3O3: Calc: C, 61.39; H, 7.30; N, 8.95. Found: C, 61.33; H, 7.38; N, 8.91.

後処理

  1. customThe ice bath was removed
  2. stirringThe mixture was stirred for 2 hours at ambient temperature
  3. customthen partitioned between saturated aqueous NaHCO3 (100 mL) and EtOAc (100 mL)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with EtOAc (3×20 mL)
  6. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customPurification by column chromatography (SiO2, 50% hexanes/EtOAc

出典と根拠

ORDレコード
ord-6b67f329bdb942ffb0863c182a12b765
出典データセット
uspto-grants-2012_05
特許番号
US08188135B2

反応ノート

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