N,N-Diethylethanamine trihydrofluoride → Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-({9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydro-quinolin-5-yl)-ethylamino]-nonyl}-methyl-amino)-bicyclo[2.2.1]hept-2-yl ester

HRID 1670901Notes

Reaction equation

HRID 1670901 reaction equation
[Si]([O:8][C@H:9]([C:45]1[CH:54]=[CH:53][C:52]([OH:55])=[C:51]2[C:46]=1[CH:47]=[CH:48][C:49](=[O:56])[NH:50]2)[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH3:44])[C@H:22]1[C@H:26]2[CH2:27][CH2:28][C@@H:23]1[C@H:24]([O:29][C:30](=[O:43])[C:31]([OH:42])([C:37]1[S:38][CH:39]=[CH:40][CH:41]=1)[C:32]1[S:33][CH:34]=[CH:35][CH:36]=1)[CH2:25]2)(C(C)(C)C)(C)C.F.F.F.C(N(CC)CC)C.C([O-])(O)=O.[Na+]>C1COCC1.C(Cl)Cl>[OH:8][C@H:9]([C:45]1[CH:54]=[CH:53][C:52]([OH:55])=[C:51]2[C:46]=1[CH:47]=[CH:48][C:49](=[O:56])[NH:50]2)[CH2:10][NH:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([CH3:44])[C@H:22]1[C@H:26]2[CH2:27][CH2:28][C@@H:23]1[C@H:24]([O:29][C:30](=[O:43])[C:31]([OH:42])([C:32]1[S:33][CH:34]=[CH:35][CH:36]=1)[C:37]1[S:38][CH:39]=[CH:40][CH:41]=1)[CH2:25]2

Participants

5

Reactant 3

HCID 175505N,N-Diethylethanamine trihydrofluorideHCID 516892Sodium BicarbonateHCID 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

Product 1

HCID 67350586Hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-({9-[(R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydro-quinolin-5-yl)-ethylamino]-nonyl}-methyl-amino)-bicyclo[2.2.1]hept-2-yl ester

Reagents, catalysts & solvents 1

HCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

A solution of hydroxy-di-thiophen-2-yl-acetic acid (1S,2R,4S,7S)-7-({9-[(R)-2-(tert-butyldimethylsilanyloxy)-2-(8-hydroxy-2-oxo-1,2-dihydro-quinolin-5-yl)ethylamino]-nonyl}methylamino)bicyclo[2.2.1]hept-2-yl ester (72 mg, 0.087 mmol) and triethylamine trihydrofluoride (60 μL, 0.37 mmol) was stirred in THF/DCM (1:1, 2 mL) at ambient temperature overnight. The reaction mixture was neutralised with satd NaHCO3 (aq) and extracted with DCM. The organic layer was concentrated to dryness to afford a green/brown oil, which was purified by preparative HPLC (system 1, 15% B+1% B/min for 20 min, then 6% B/min for 10 min). The fractions containing pure product were concentrated, neutralised with satd NaHCO3 (aq), and extracted with THF. After concentration in vacuo a light brown oil was obtained.

Workup

  1. extractionextracted with DCM
  2. concentrationThe organic layer was concentrated to dryness
  3. customto afford a green/brown oil, which
  4. customwas purified by preparative HPLC (system 1, 15% B+1% B/min for 20 min
  5. additionThe fractions containing pure product
  6. concentrationwere concentrated
  7. extractionextracted with THF
  8. concentrationAfter concentration in vacuo a light brown oil
  9. customwas obtained

Sources & evidence

ORD record
ord-21c9d56015554af79df7743c0e6fcc33
Source dataset
uspto-grants-2011_08
Patent number
US07994211B2

Reaction notes

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