Sodium Bicarbonate → (9-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 446429

반응식

HRID 446429 반응식
[Si:1]([O:8][CH2:9][CH2:10][C:11]1[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH:14]=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.[CH:27]([C:30]1[S:31][CH:32]=[C:33]([C:35]([N:37]2[CH2:42][C:41]3([CH2:47][CH2:46][NH:45][CH2:44][CH2:43]3)[O:40][CH2:39][CH2:38]2)=[O:36])[N:34]=1)([CH3:29])[CH3:28].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[C:12]([F:19])=[C:13]([CH:16]=[CH:17][CH:18]=1)[CH2:14][N:45]1[CH2:46][CH2:47][C:41]2([O:40][CH2:39][CH2:38][N:37]([C:35]([C:33]3[N:34]=[C:30]([CH:27]([CH3:28])[CH3:29])[S:31][CH:32]=3)=[O:36])[CH2:42]2)[CH2:43][CH2:44]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579891643-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzaldehyde2회HCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

생성물 1

HCID 58168600(9-(3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzyl)-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

3-(2-(tert-Butyldimethylsilyloxy)ethyl)-2-fluorobenzaldehyde [Aromatic Intermediate 5] (4.07 g) was added to (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate [Example 1, step b] (6.10 g) in a mixture of N-methyl-2-pyrrolidinone (50 mL) and acetic acid (0.83 mL) and stirred for 30 min. Sodium triacetoxyborohydride (4.58 g) was then added and the mixture stirred overnight. The reaction mixture was poured into water (100 mL), the pH was adjusted to 8 using saturated sodium bicarbonate solution, and the mixture was extracted with ethyl acetate (3×100 mL). The combined organic phases were washed with water (3×100 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by flash silica chromatography using 77.5:17.5:5 isohexane:ethyl acetate:triethylamine as solvent to give the subtitled compound as a clear oil. Yield 5.35 g.

후처리

  1. stirringthe mixture stirred overnight
  2. extractionthe mixture was extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic phases were washed with water (3×100 mL) and brine (100 mL)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by flash silica chromatography

출처 및 근거

ORD 기록
ord-92c9d161fa2e49ab8fc5cf6638fabb30
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08476265B2

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