Acetic Acid → (R)-5-(1-(tert-Butyldimethylsilyloxy)-2-(3-(3-(4-(2-methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propoxy)benzylamino)ethyl)-8-hydroxyquinolin-2(1H)-one

HRID 1689453Notes

Reaction equation

HRID 1689453 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH3:15][C:16]1[S:17][CH:18]=[C:19]([C:21]([N:23]2[CH2:28][C:27]3([CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][O:37][C:38]4[CH:39]=[C:40]([CH:43]=[CH:44][CH:45]=4)[CH:41]=O)[CH2:30][CH2:29]3)[O:26][CH2:25][CH2:24]2)=[O:22])[N:20]=1.[NH2:46][CH2:47][C@@H:48]([C:57]1[CH:66]=[CH:65][C:64]([OH:67])=[C:63]2[C:58]=1[CH:59]=[CH:60][C:61](=[O:68])[NH:62]2)[O:49][Si:50]([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51].C(O)(=O)C>CO>[Si:50]([O:49][C@H:48]([C:57]1[CH:66]=[CH:65][C:64]([OH:67])=[C:63]2[C:58]=1[CH:59]=[CH:60][C:61](=[O:68])[NH:62]2)[CH2:47][NH:46][CH2:41][C:40]1[CH:43]=[CH:44][CH:45]=[C:38]([O:37][CH2:36][CH2:35][CH2:34][N:31]2[CH2:32][CH2:33][C:27]3([O:26][CH2:25][CH2:24][N:23]([C:21]([C:19]4[N:20]=[C:16]([CH3:15])[S:17][CH:18]=4)=[O:22])[CH2:28]3)[CH2:29][CH2:30]2)[CH:39]=1)([C:53]([CH3:56])([CH3:55])[CH3:54])([CH3:52])[CH3:51]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579889423-(3-(4-(2-Methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propoxy)benzaldehydeHCID 59023604(R)-5-(2-Amino-1-((tert-butyldimethylsilyl)oxy)ethyl)-8-hydroxyquinolin-2(1H)-one

Product 1

HCID 67292255(R)-5-(1-(tert-Butyldimethylsilyloxy)-2-(3-(3-(4-(2-methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propoxy)benzylamino)ethyl)-8-hydroxyquinolin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
20 °C

Procedure

Sodium triacetoxyborohydride (0.113 g) was added in one portion to a stirred solution at 0° C. of 3-(3-(4-(2-methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)propoxy)benzaldehyde (example 95, step b) (0.157 g), (R)-5-(2-amino-1-(tert-butyldimethylsilyloxy)ethyl)-8-hydroxyquinolin-2(1H)-one (WO2004106333) (0.118 g) and acetic acid (0.020 mL) in methanol (7 mL). The resulting mixture was stirred at 20° C. for 2 hours. Most of the methanol was evaporated under reduced pressure and the residue was partitioned between ethyl acetate and aqueous phosphate buffer (pH=7.2), the organic layer was dried over sodium sulphate, filtered and the solvent evaporated under reduced pressure. The crude product was purified by flash silica chromatography using 8% methanol and 1% ‘880’ aqueous ammonia in dichloromethane as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.160 g.

Workup

  1. customMost of the methanol was evaporated under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and aqueous phosphate buffer (pH=7.2)
  3. dry with materialthe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. customthe solvent evaporated under reduced pressure
  6. customThe crude product was purified by flash silica chromatography
  7. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-09ceb3289b27427fb70b9a0962c14195
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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