Sodium Bicarbonate → (9-((5-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophen-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471306노트

반응식

HRID 471306 반응식
[Si:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][CH:14]=[C:13]([CH:16]=O)[CH:12]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH:25]([C:28]1[S:29][CH:30]=[C:31]([C:33]([N:35]2[CH2:40][C:39]3([CH2:45][CH2:44][NH:43][CH2:42][CH2:41]3)[O:38][CH2:37][CH2:36]2)=[O:34])[N:32]=1)([CH3:27])[CH3:26].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.C(O)(=O)C.O>[Si:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][CH:14]=[C:13]([CH2:16][N:43]2[CH2:44][CH2:45][C:39]3([O:38][CH2:37][CH2:36][N:35]([C:33]([C:31]4[N:32]=[C:28]([CH:25]([CH3:26])[CH3:27])[S:29][CH:30]=4)=[O:34])[CH2:40]3)[CH2:41][CH2:42]2)[CH:12]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

참가 물질

8

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579889035-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophene-3-carbaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

생성물 1

HCID 57988978(9-((5-(2-(Tert-butyldimethylsilyloxy)ethyl)thiophen-3-yl)methyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

시약·촉매·용매 3

HCID 176Acetic Acid용매HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

5-(2-(tert-butyldimethylsilyloxy)ethyl)thiophene-3-carbaldehyde (0.6 g) (example 278, step c) was added to (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (0.94 g) (example 22, step b) in a mixture of N-methyl-2-pyrrolidinone (5 mL) and acetic acid (0.13 mL) and stirred for 30 min. Sodium triacetoxyborohydride (0.71 g) was then added and the mixture stirred overnight. The reaction was poured into water (100 mL), the pH was adjusted to 8 using saturated sodium bicarbonate solution and the resulting aqueous solution extracted with ethyl acetate (3×100 mL). The combined organic solutions were washed with water (3×100 mL), brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography eluting with 77.5:17.5:5 i-hexane:ethyl acetate:triethylamine to 47.5:47.5:5 i-hexane:ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated in vacuo to give the subtitled compound as a clear oil. Yield 0.8 g.

후처리

  1. stirringthe mixture stirred overnight
  2. extractionthe resulting aqueous solution extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic solutions were washed with water (3×100 mL), brine (100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 77.5:17.5:5 i-hexane
  9. additionThe fractions containing product
  10. customevaporated in vacuo

출처 및 근거

ORD 기록
ord-1cb927f1056c46559a4f2c987c810146
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629271B2

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