Methanol → {8-Fluoro-1,4-dioxaspiro[4.5]decan-8-yl}methanol

HRID 75723ノート

反応式

HRID 75723 の反応式
[F:1][C:2]1([C:12](OCC)=[O:13])[CH2:11][CH2:10][C:5]2([O:9][CH2:8][CH2:7][O:6]2)[CH2:4][CH2:3]1.[Li+].[BH4-].CO.C([O-])(O)=O.[Na+]>C1COCC1>[F:1][C:2]1([CH2:12][OH:13])[CH2:11][CH2:10][C:5]2([O:6][CH2:7][CH2:8][O:9]2)[CH2:4][CH2:3]1

参加物

6

反応物 4

HCID 887Methanol2 回HCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 67960160Ethyl 8-fluoro-1,4-dioxaspiro[4.5]decane-8-carboxylate

生成物 1

HCID 67225989{8-Fluoro-1,4-dioxaspiro[4.5]decan-8-yl}methanol収率 56%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of crude ethyl 8-fluoro-1,4-dioxaspiro[4.5]decane-8-carboxylate, Intermediate 30, (16.26 g, 70 mmol calculated based on previous reaction, 1 equiv) in THF (100 mL) was added LiBH4 (45.5 mL of a 2 M solution in THF, 91 mmol, 1.3 equiv) followed by MeOH (3.68 mL, 91 mmol, 1.3 equiv). Significant warming was observed following MeOH addition. The reaction was stirred 30 min at which time TLC showed no ester remaining. The reaction was poured into a saturated aqueous solution of NaHCO3 and the aqueous solution was extracted with ether (×3). The combined ether layers were dried (MgSO4) and concentrated in vacuo. The crude product was purified by silica gel chromatography (30-90% ethyl acetate/hexane) to provide the title compound (7.50 g, 56% yield for 2 steps) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 3.90-4.03 (m, 4H), 3.64 (d, J=6.78 Hz, 1H), 3.59 (d, J=6.78 Hz, 1H), 1.97-2.09 (m, 2H), 1.84-1.95 (m, 2H), 1.62-1.80 (m, 4H); 19F NMR (376 MHz, CDCl3) δ ppm −171.25 (br. s., 1F).

後処理

  1. temperatureSignificant warming
  2. extractionthe aqueous solution was extracted with ether (×3)
  3. dry with materialThe combined ether layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by silica gel chromatography (30-90% ethyl acetate/hexane)

出典と根拠

ORDレコード
ord-5a876810e4d94988af54b4bb03411aa1
出典データセット
uspto-grants-2014_09
特許番号
US08835411B2

反応ノート

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