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 1689527Notes

Reaction equation

HRID 1689527 reaction equation
[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]

Participants

8

Reactant 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

Product 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

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-24c65cd24dcd46aaab21a12942f94078
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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