Sodium Bicarbonate → (9-(2-Chloro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 471186Notes

Reaction equation

HRID 471186 reaction equation
FC(F)(F)C(O)=O.[CH:8]([C:11]1[S:12][CH:13]=[C:14]([C:16]([N:18]2[CH2:23][C:22]3([CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)[O:21][CH2:20][CH2:19]2)=[O:17])[N:15]=1)([CH3:10])[CH3:9].[Cl:29][C:30]1[C:37]([CH2:38][CH2:39][OH:40])=[CH:36][CH:35]=[CH:34][C:31]=1[CH:32]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CN1C(=O)CCC1.C(O)(=O)C>[Cl:29][C:30]1[C:37]([CH2:38][CH2:39][OH:40])=[CH:36][CH:35]=[CH:34][C:31]=1[CH2:32][N:26]1[CH2:25][CH2:24][C:22]2([O:21][CH2:20][CH2:19][N:18]([C:16]([C:14]3[N:15]=[C:11]([CH:8]([CH3:10])[CH3:9])[S:12][CH:13]=3)=[O:17])[CH2:23]2)[CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579889292-Chloro-3-(2-hydroxyethyl)benzaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 46240302(9-(2-Chloro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

A solution of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.325 g) in NMP (3 mL) was treated with acetic acid (0.067 mL) and stirred for 5 minutes. A solution of 2-chloro-3-(2-hydroxyethyl)benzaldehyde (example 80, step d) (0.217 g) in NMP (4 mL) was then added, the resulting solution was stirred for 1 hour and then treated with sodium triacetoxyborohydride (1.025 g). The mixture was stirred overnight at room temperature, then poured into saturated sodium bicarbonate and extracted twice with ethyl acetate. The combined extracts were washed three times with water, once with brine, then dried over anhydrous magnesium sulphate and purified by flash chromatography on silica eluted with 1:2:97 triethylamine:methanol:dichloromethane to afford the subtitled compound as a colourless gum. Yield 0.411 g.

Workup

  1. stirringthe resulting solution was stirred for 1 hour
  2. stirringThe mixture was stirred overnight at room temperature
  3. extractionextracted twice with ethyl acetate
  4. washThe combined extracts were washed three times with water
  5. dry with materialonce with brine, then dried over anhydrous magnesium sulphate
  6. custompurified by flash chromatography on silica
  7. washeluted with 1:2:97 triethylamine

Sources & evidence

ORD record
ord-8d1b77e45e364b9e878066b3fcdd0cca
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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