Acetic Acid → (9-(2-Fluoro-5-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471063

反応式

HRID 471063 の反応式
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[F:15][C:16]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][OH:26])=[CH:20][C:17]=1[CH:18]=O.FC(F)(F)C(O)=O.[CH:34]([C:37]1[S:38][CH:39]=[C:40]([C:42]([N:44]2[CH2:49][C:48]3([CH2:54][CH2:53][NH:52][CH2:51][CH2:50]3)[O:47][CH2:46][CH2:45]2)=[O:43])[N:41]=1)([CH3:36])[CH3:35].C(O)(=O)C>CN1C(=O)CCC1.C(OCC)(=O)C>[F:15][C:16]1[CH:23]=[CH:22][C:21]([CH2:24][CH2:25][OH:26])=[CH:20][C:17]=1[CH2:18][N:52]1[CH2:53][CH2:54][C:48]2([O:47][CH2:46][CH2:45][N:44]([C:42]([C:40]3[N:41]=[C:37]([CH:34]([CH3:35])[CH3:36])[S:38][CH:39]=3)=[O:43])[CH2:49]2)[CH2:50][CH2:51]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydride2 回HCID 579893302-Fluoro-5-(2-hydroxyethyl)benzaldehyde2 回HCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

生成物 1

HCID 57989245(9-(2-Fluoro-5-(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 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

実験手順

Sodium triacetoxyborohydride (0.339 g) was added to a stirred solution of 2-fluoro-5-(2-hydroxyethyl)benzaldehyde (example 40, step a) (0.135 g), (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.339 g) and acetic acid (0.046 mL) in NMP (7 mL). After 16 h, more 2-fluoro-5-(2-hydroxyethyl)benzaldehyde (example 40, step a) (0.135 g) was added followed by sodium triacetoxyborohydride (0.339 g). After 2 h, the reaction mixture was diluted with ethyl acetate (60 mL) and washed with saturated sodium bicarbonate solution (30 mL). The aqueous layer was extracted with ethyl acetate. The combined ethyl acetate solution was evaporated in vacuo. Purification was by silica gel chromatography eluting with ethyl acetate:triethylamine, 10:1 to give the subtitled compound as a gum that contained NMP. The NMP was removed by applying the gum to a 10 g SCX cartridge eluting first with methanol and then 20% ‘880’ aqueous ammonia in methanol to collect the subtitled compound. The solution was evaporated to dryness and the resulting gum applied to a silica gel column eluting with ethyl acetate:triethylamine, 10:1 to give the subtitled compound as a gum. Yield 0.31 g.

後処理

  1. waitAfter 2 h
  2. washwashed with saturated sodium bicarbonate solution (30 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. customThe combined ethyl acetate solution was evaporated in vacuo
  5. customPurification
  6. washeluting with ethyl acetate

出典と根拠

ORDレコード
ord-6315c35740d4409582f798926d9fd44d
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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