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

HRID 1689393Notes

Reaction equation

HRID 1689393 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[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][C:31]=1[CH2:38][CH2:39][OH:40].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[CH:37]=[CH:36][C:33]([CH2:34][N:26]2[CH2:25][CH2:24][C:22]3([O:21][CH2:20][CH2:19][N:18]([C:16]([C:14]4[N:15]=[C:11]([CH:8]([CH3:10])[CH3:9])[S:12][CH:13]=4)=[O:17])[CH2:23]3)[CH2:28][CH2:27]2)=[CH:32][C:31]=1[CH2:38][CH2:39][OH:40]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydride2×HCID 579890474-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 57989207(9-(4-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) (0.178 g) in NMP (2 mL) was treated with acetic acid (0.032 mL) and stirred for 5 minutes. A solution of 4-chloro-3-(2-hydroxyethyl)benzaldehyde (example 75, step c) (0.154 g) in NMP (3 mL) was then added, the resulting solution was stirred for 1 hour and was then treated with sodium triacetoxyborohydride (0.181 g) and stirred overnight at room temperature. More sodium triacetoxyborohydride (0.404 g) was added and the mixture was stirred for an additional 6 hours, 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 0.157 g.

Workup

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

Sources & evidence

ORD record
ord-26c250676acb4494b08bd94b822d7d36
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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