Acetic Acid → (9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471092

反応式

HRID 471092 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.[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([N:30]2[CH2:35][C:34]3([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[O:33][CH2:32][CH2:31]2)=[O:29])[N:27]=1)([CH3:22])[CH3:21].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1CCCC1=O.C(#N)C>[F:1][C:2]1[C:9]([CH2:10][CH2:11][OH:12])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:38]1[CH2:39][CH2:40][C:34]2([O:33][CH2:32][CH2:31][N:30]([C:28]([C:26]3[N:27]=[C:23]([CH:20]([CH3:21])[CH3:22])[S:24][CH:25]=3)=[O:29])[CH2:35]2)[CH2:36][CH2:37]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579892682-Fluoro-3-(2-hydroxyethyl)benzaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

生成物 1

HCID 57989273(9-(2-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

2-Fluoro-3-(2-hydroxyethyl)benzaldehyde (example 48, step a) (0.19 g) was added to a solution of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.32 g) and acetic acid (0.043 mL) in N-methyl-2-pyrrolidinone (5 mL). The resulting mixture was stirred for 1 h then sodium triacetoxyborohydride (0.24 g) was added portionwise over 5 min. The resulting mixture was stirred overnight, diluted with acetonitrile (20 mL) and applied to a SCX cartridge (10 g Varian, pre-wetted with acetonitrile (50 mL)). The cartridge was washed with acetonitrile (50 mL) and eluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL). The eluent was evaporated, azeotroped with toluene and purified by silica gel chromatography eluting with 77.5:17.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a yellow gum. Yield 0.33 g.

後処理

  1. stirringThe resulting mixture was stirred overnight
  2. washThe cartridge was washed with acetonitrile (50 mL)
  3. washeluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL)
  4. customThe eluent was evaporated
  5. customazeotroped with toluene
  6. custompurified by silica gel chromatography
  7. washeluting with 77.5:17.5:5 isohexane
  8. additionThe fractions containing product
  9. customevaporated

出典と根拠

ORDレコード
ord-da1f2ca742d846279dc0537a50a33c93
出典データセット
uspto-grants-2014_01
特許番号
US08629271B2

関連ノート

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