Sodium triacetoxyborohydride → Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-({9-[(R)-2-(tert-butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}methyl-amino)bicyclo[2.2.1]hept-2-yl ester

HRID 1670900Notes

Reaction equation

HRID 1670900 reaction equation
[CH3:1][N:2]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH:33]=O)[C@H:3]1[C@H:7]2[CH2:8][CH2:9][C@@H:4]1[C@H:5]([O:10][C:11](=[O:24])[C:12]([OH:23])([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)[C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[CH2:6]2.[NH2:35][CH2:36][C@@H:37]([C:46]1[CH:55]=[CH:54][C:53]([OH:56])=[C:52]2[C:47]=1[CH:48]=[CH:49][C:50](=[O:57])[NH:51]2)[O:38][Si:39]([C:42]([CH3:45])([CH3:44])[CH3:43])([CH3:41])[CH3:40].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.ClCCCl>[C:42]([Si:39]([CH3:41])([CH3:40])[O:38][C@H:37]([C:46]1[CH:55]=[CH:54][C:53]([OH:56])=[C:52]2[C:47]=1[CH:48]=[CH:49][C:50](=[O:57])[NH:51]2)[CH2:36][NH:35][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][N:2]([CH3:1])[C@H:3]1[C@H:7]2[CH2:8][CH2:9][C@@H:4]1[C@H:5]([O:10][C:11](=[O:24])[C:12]([OH:23])([C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)[C:13]1[S:14][CH:15]=[CH:16][CH:17]=1)[CH2:6]2)([CH3:45])([CH3:44])[CH3:43]

Participants

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59023604(R)-5-(2-Amino-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-hydroxyquinolin-2(1H)-oneHCID 86642393hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-[methyl-(9-oxo-nonyl)amino]bicyclo[2.2.1]hept-2-yl ester

Product 1

HCID 67350381Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-({9-[(R)-2-(tert-butyldimethyl-silanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethylamino]nonyl}methyl-amino)bicyclo[2.2.1]hept-2-yl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Procedure

A mixture of hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-[methyl-(9-oxo-nonyl)amino]bicyclo[2.2.1]hept-2-yl ester (max 0.73 mmol), 5-[(R)-2-amino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-hydroxy-1H-quinolin-2-one (245 mg, 0.73 mmol), sodium triacetoxyborohydride (186 mg, 0.88 mmol), and acetic acid (2 drops) in dry 1,2-dichloroethane was stirred at ambient temperature overnight. The reaction mixture was partitioned between DCM and satd NaHCO3 (aq). The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo to afford a dark green/brown gum that solidified on standing, which was purified by preparative HPLC (system 2, 35% B+1% B/min). The fractions containing pure product were concentrated, neutralised with satd NaHCO3 (aq), and extracted with DCM. After concentration in vacuo a green/brown oil was obtained.

Workup

  1. customThe reaction mixture was partitioned between DCM and satd NaHCO3 (aq)
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto afford a dark green/brown gum that
  6. customwas purified by preparative HPLC (system 2, 35% B+1% B/min)
  7. additionThe fractions containing pure product
  8. concentrationwere concentrated
  9. extractionextracted with DCM
  10. concentrationAfter concentration in vacuo a green/brown oil
  11. customwas obtained

Sources & evidence

ORD record
ord-ce9824fd5b8b48ad92f485b7fcc98d1e
Source dataset
uspto-grants-2011_08
Patent number
US07994211B2

Reaction notes

Loading…