Acetic Acid → (9-(2-(3-(2-Hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

HRID 1689252Notes

Reaction equation

HRID 1689252 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[O:7][CH2:8][CH:9]=O.FC(F)(F)C(O)=O.[CH3:21][C:22]1[S:23][CH:24]=[C:25]([C:27]([N:29]2[CH2:34][C:33]3([CH2:39][CH2:38][NH:37][CH2:36][CH2:35]3)[O:32][CH2:31][CH2:30]2)=[O:28])[N:26]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO>[OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[O:7][CH2:8][CH2:9][N:37]1[CH2:38][CH2:39][C:33]2([O:32][CH2:31][CH2:30][N:29]([C:27]([C:25]3[N:26]=[C:22]([CH3:21])[S:23][CH:24]=3)=[O:28])[CH2:34]2)[CH2:35][CH2:36]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 579889682-(3-(2-Hydroxyethyl)phenoxy)acetaldehydeHCID 66964121(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989375(9-(2-(3-(2-Hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of 2-(3-(2-hydroxyethyl)phenoxy)acetaldehyde (example 24, step b) (0.143 g) and (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.314 g) in methanol (10 mL) was treated with acetic acid (0.045 mL) and stirred at room temperature for 30 minutes. The mixture was cooled in ice-water, treated with sodium triacetoxyborohydride (0.254 g) and stirred over 3 days, allowing the ice-bath to expire. The resulting solution was purified by flash chromatography on silica eluted with 1:15:84 triethylamine:methanol:dichloromethane to afford the crude product (0.243 g). A second purification by flash chromatography on silica eluted with 1:5:94 triethylamine:methanol:dichloromethane afforded the slightly impure subtitled compound as a brown gum. Yield 0.122 g.

Workup

  1. stirringstirred over 3 days
  2. customThe resulting solution was purified by flash chromatography on silica
  3. washeluted with 1:15:84 triethylamine
  4. custommethanol:dichloromethane to afford the crude product (0.243 g)
  5. customA second purification by flash chromatography on silica
  6. washeluted with 1:5:94 triethylamine

Sources & evidence

ORD record
ord-663ca2f728ac4e8e94f3463c7b03cf32
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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