Sodium Bicarbonate → 2,2,2-Trifluoro-1-(9-(2-fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone

HRID 1689372

反応式

HRID 1689372 の反応式
[F:1][C:2]1[C:9]([CH2:10][CH2:11][OH:12])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.FC(F)(F)C(O)=O.[F:20][C:21]([F:36])([F:35])[C:22]([N:24]1[CH2:29][C:28]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[O:27][CH2:26][CH2:25]1)=[O:23].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN1CCCC1=O.O.C(O)(=O)C>[F:36][C:21]([F:20])([F:35])[C:22]([N:24]1[CH2:29][C:28]2([CH2:34][CH2:33][N:32]([CH2:4][C:3]3[CH:6]=[CH:7][CH:8]=[C:9]([CH2:10][CH2:11][OH:12])[C:2]=3[F:1])[CH2:31][CH2:30]2)[O:27][CH2:26][CH2:25]1)=[O:23]

参加物

8

反応物 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579892682-Fluoro-3-(2-hydroxyethyl)benzaldehydeHCID 866367502,2,2-Trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate

生成物 1

HCID 579893822,2,2-Trifluoro-1-(9-(2-fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone

試薬・触媒・溶媒 3

HCID 176Acetic Acid溶媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

2-Fluoro-3-(2-hydroxyethyl)benzaldehyde (example 48, step a) (1.05 g) was added to a solution of 2,2,2-trifluoro-1-(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)ethanone trifluoroacetate (example 12, step d) (2.08 g) and acetic acid (0.33 mL) in N-methyl-2-pyrrolidinone (10 mL). The resulting mixture was stirred for 15 min then cooled in an ice bath. Sodium triacetoxyborohydride (1.81 g) was then added and the mixture stirred overnight. The reaction was poured into a mixture of saturated sodium hydrogen carbonate solution (20 mL) and water (100 mL). The aqueous was extracted with ethyl acetate (3×100 mL). The combined organics were washed with water (50 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 4:1 isohexane:ethyl acetate+5% triethylamine to ethyl acetate+5% triethylamine gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a clear oil. Yield 1.9 g. Used immediately.

後処理

  1. temperaturethen cooled in an ice bath
  2. stirringthe mixture stirred overnight
  3. extractionThe aqueous was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organics were washed with water (50 mL) and brine (100 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with 4:1 isohexane
  10. additionThe fractions containing product
  11. customevaporated

出典と根拠

ORDレコード
ord-fdbc8c2db36746338772f5bc67ffc215
出典データセット
uspto-grants-2012_04
特許番号
US08148373B2

関連ノート

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