Sodium Bicarbonate → tert-Butyl (R)-2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl((R)-1-(3-((4-(5-isopropylthiophene-3-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)propan-2-yl)carbamate

HRID 1689527노트

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HRID 1689527 반응식
[Si:1]([O:8][C@H:9]([C:30]1[CH:39]=[CH:38][C:37]([OH:40])=[C:36]2[C:31]=1[CH:32]=[CH:33][C:34](=[O:41])[NH:35]2)[CH2:10][N:11]([C@H:19]([CH3:29])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=O)[CH:22]=1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH:42]([C:45]1[S:49][CH:48]=[C:47]([C:50]([N:52]2[CH2:57][C:56]3([CH2:62][CH2:61][NH:60][CH2:59][CH2:58]3)[O:55][CH2:54][CH2:53]2)=[O:51])[CH:46]=1)([CH3:44])[CH3:43].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>O.C(O)(=O)C.CN1CCCC1=O>[Si:1]([O:8][C@H:9]([C:30]1[CH:39]=[CH:38][C:37]([OH:40])=[C:36]2[C:31]=1[CH:32]=[CH:33][C:34](=[O:41])[NH:35]2)[CH2:10][N:11]([C@H:19]([CH3:29])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH2:27][N:60]2[CH2:59][CH2:58][C:56]3([O:55][CH2:54][CH2:53][N:52]([C:50]([C:47]4[CH:46]=[C:45]([CH:42]([CH3:44])[CH3:43])[S:49][CH:48]=4)=[O:51])[CH2:57]3)[CH2:62][CH2:61]2)[CH:22]=1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:15])[CH3:16])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

참가 물질

8

반응물 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57989215(5-Isopropylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanoneHCID 57989338tert-Butyl (R)-2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl((R)-1-(3-formylphenyl)propan-2-yl)carbamate

생성물 1

HCID 57989027tert-Butyl (R)-2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl((R)-1-(3-((4-(5-isopropylthiophene-3-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)propan-2-yl)carbamate

시약·촉매·용매 3

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

실험 절차

tert-Butyl (R)-2-(tert-butyldimethylsilyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl((R)-1-(3-formylphenyl)propan-2-yl)carbamate (Example 276, step i) (0.476 g) was treated with (5-isopropylthiophen-3-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone (Example 275, step i) (0.296 g), N-methyl-2-pyrrolidinone (20 mL), acetic acid (0.052 mL) and sodium triacetoxyborohydride (0.294 g), and the mixture was stirred at room temperature overnight. The solution was poured into a mixture of saturated sodium bicarbonate solution and water and extracted three times with diethyl ether. The combined extracts were washed with water and brine, dried (MgSO4) and concentrated in vacuo, then purified by flash chromatography on silica eluted with 1:5:94 NEt3:MeOH:DCM to afford the subtitled compound. Yield 0.471 g.

후처리

  1. extractionextracted three times with diethyl ether
  2. washThe combined extracts were washed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. custompurified by flash chromatography on silica
  6. washeluted with 1:5:94 NEt3

출처 및 근거

ORD 기록
ord-24c65cd24dcd46aaab21a12942f94078
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08148373B2

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