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

HRID 471059
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HRID 471059 반응식
[Si:1]([O:8][CH2:9][CH:10]([C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=O)[F:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(O)(=O)C.FC(F)(F)C(O)=O.[CH:31]([C:34]1[S:35][CH:36]=[C:37]([C:39]([N:41]2[CH2:46][C:45]3([CH2:51][CH2:50][NH:49][CH2:48][CH2:47]3)[O:44][CH2:43][CH2:42]2)=[O:40])[N:38]=1)([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[Si:1]([O:8][CH2:9][CH:10]([C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15][N:49]1[CH2:50][CH2:51][C:45]2([O:44][CH2:43][CH2:42][N:41]([C:39]([C:37]3[N:38]=[C:34]([CH:31]([CH3:32])[CH3:33])[S:35][CH:36]=3)=[O:40])[CH2:46]2)[CH2:47][CH2:48]1)[F:11])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
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참가 물질

6

반응물 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579892013-(2-(tert-Butyldimethylsilyloxy)-1-fluoroethyl)benzaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

생성물 1

HCID 57989307(9-(3-(2-(tert-Butyldimethylsilyloxy)-1-fluoroethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of 3-(2-(tert-butyldimethylsilyloxy)-1-fluoroethyl)benzaldehyde (example 39, step d) (0.329 g) in MeOH (4 mL) was treated with acetic acid (0.055 mL) followed by (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.408 g) and stirred at room temperature for 5 minutes. The solution was cooled in an ice-water bath, treated with sodium triacetoxyborohydride (0.309 g), stirred in ice-water for 135 minutes, then removed from the cooling bath and stirred at room temperature for a further 65 minutes. The solution was cooled back down in ice-water, treated with more sodium triacetoxyborohydride (0.310 g) and stirred in ice-water for 75 minutes. More sodium triacetoxyborohydride (0.312 g) was added and the mixture was stirred for 70 minutes. More sodium triacetoxyborohydride (0.619 g) was added and the mixture was stirred overnight, allowing the cooling bath to slowly expire. The next day, more sodium triacetoxyborohydride (0.307 g) was added and the mixture was stirred for 70 minutes. More acetic acid (0.055 mL) was added and the mixture was stirred for 80 minutes. The mixture was warmed to 40° C. and stirred at that temperature for 25 minutes, then it was concentrated onto flash silica in vacuo. The residue was purified by flash chromatography on silica eluted with 5% methanol in dichloromethane to afford the subtitled compound as a sticky white solid. Yield 0.344 g.

후처리

  1. temperatureThe solution was cooled in an ice-water bath
  2. customremoved from the cooling bath
  3. stirringstirred at room temperature for a further 65 minutes
  4. temperatureThe solution was cooled back down in ice-water
  5. additiontreated with more sodium triacetoxyborohydride (0.310 g)
  6. stirringstirred in ice-water for 75 minutes
  7. additionMore sodium triacetoxyborohydride (0.312 g) was added
  8. stirringthe mixture was stirred for 70 minutes
  9. additionMore sodium triacetoxyborohydride (0.619 g) was added
  10. stirringthe mixture was stirred overnight
  11. additionThe next day, more sodium triacetoxyborohydride (0.307 g) was added
  12. stirringthe mixture was stirred for 70 minutes
  13. additionMore acetic acid (0.055 mL) was added
  14. stirringthe mixture was stirred for 80 minutes
  15. temperatureThe mixture was warmed to 40° C.
  16. stirringstirred at that temperature for 25 minutes
  17. concentrationit was concentrated onto flash silica in vacuo
  18. customThe residue was purified by flash chromatography on silica
  19. washeluted with 5% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-339705158ba9449ab8b5a869e2dcf34a
출처 데이터셋
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08629271B2

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