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

HRID 75723노트

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HRID 75723 반응식
[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

참가 물질

6

반응물 4

HCID 887Methanol2회HCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 67960160Ethyl 8-fluoro-1,4-dioxaspiro[4.5]decane-8-carboxylate

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-5a876810e4d94988af54b4bb03411aa1
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835411B2

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