Acetic Acid → HCID 57988996, compound

HRID 1689418Notes

Reaction equation

HRID 1689418 reaction equation
[NH2:1][CH2:2][C@@H:3]([C:12]1[CH:21]=[CH:20][C:19]([OH:22])=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16](=[O:23])[NH:17]2)[O:4][Si:5]([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6].C(O)(=O)C.[Cl:28][C:29]1[C:34]([CH2:35][N:36]2[CH2:56][CH2:55][C:39]3([O:44][CH2:43][CH2:42][N:41]([C:45]([C:47]4[N:48]=[C:49]([CH:52]([CH3:54])[CH3:53])[S:50][CH:51]=4)=[O:46])[CH2:40]3)[CH2:38][CH2:37]2)=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:57][CH:58]=O.C([BH3-])#N.[Na+]>CO>[Si:5]([O:4][C@H:3]([C:12]1[CH:21]=[CH:20][C:19]([OH:22])=[C:18]2[C:13]=1[CH:14]=[CH:15][C:16](=[O:23])[NH:17]2)[CH2:2][NH:1][CH2:58][CH2:57][C:30]1[CH:31]=[CH:32][CH:33]=[C:34]([CH2:35][N:36]2[CH2:37][CH2:38][C:39]3([O:44][CH2:43][CH2:42][N:41]([C:45]([C:47]4[N:48]=[C:49]([CH:52]([CH3:53])[CH3:54])[S:50][CH:51]=4)=[O:46])[CH2:40]3)[CH2:55][CH2:56]2)[C:29]=1[Cl:28])([C:8]([CH3:11])([CH3:10])[CH3:9])([CH3:7])[CH3:6]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 579889712-(2-Chloro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)acetaldehydeHCID 59023604(R)-5-(2-Amino-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-hydroxyquinolin-2(1H)-one

Product 1

HCID 57988996HCID 57988996, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of (R)-5-(2-amino-1-(tert-butyldimethylsilyloxy)ethyl)-8-hydroxyquinolin-2(1H)-one (WO2004106333) (0.261 g) in methanol (2 mL) was treated with acetic acid (0.030 mL) and stirred for 10 minutes. A solution of 2-(2-chloro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenyl)acetaldehyde (example 80, step f) (0.247 g) in methanol (3 mL) was then added, and the resulting mixture was stirred at room temperature for 10 minutes, before cooling in ice-water and treating with sodium cyanoborohydride (0.102 g). The cooling bath was removed and the mixture was stirred at room temperature overnight. More sodium cyanoborohydride (0.101 g) was added, and the mixture was stirred over a second night. The solution was then concentrated onto flash silica in vacuo, and the resulting powder was purified by flash chromatography on silica eluted with 1:3:96 to 1:5:94 triethylamine:methanol:dichloromethane to afford the subtitled compound as a yellow oil. Yield 0.130 g.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 10 minutes
  2. customThe cooling bath was removed
  3. stirringthe mixture was stirred at room temperature overnight
  4. additionMore sodium cyanoborohydride (0.101 g) was added
  5. stirringthe mixture was stirred over a second night
  6. concentrationThe solution was then concentrated onto flash silica in vacuo
  7. customthe resulting powder was purified by flash chromatography on silica
  8. washeluted with 1:3:96 to 1:5:94 triethylamine

Sources & evidence

ORD record
ord-562b9618bbb14e7a82a69f93eefcf9f7
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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