Triethylamine → 3-(2-(4-(2-Methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzaldehyde

HRID 470981Notes

Reaction equation

HRID 470981 reaction equation
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH:15]=[O:16])[CH:10]=1)(=O)=O.FC(F)(F)C(O)=O.[CH3:24][C:25]1[S:26][CH:27]=[C:28]([C:30]([N:32]2[CH2:37][C:36]3([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]3)[O:35][CH2:34][CH2:33]2)=[O:31])[N:29]=1.C(N(CC)CC)C>C(#N)C>[CH3:24][C:25]1[S:26][CH:27]=[C:28]([C:30]([N:32]2[CH2:37][C:36]3([CH2:42][CH2:41][N:40]([CH2:6][CH2:7][O:8][C:9]4[CH:10]=[C:11]([CH:12]=[CH:13][CH:14]=4)[CH:15]=[O:16])[CH2:39][CH2:38]3)[O:35][CH2:34][CH2:33]2)=[O:31])[N:29]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 579893722-(3-Formylphenoxy)ethyl methanesulfonateHCID 66964121(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 579889763-(2-(4-(2-Methylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethoxy)benzaldehyde

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
65 °C

Procedure

2-(3-Formylphenoxy)ethyl methanesulfonate (example 10, step a) (0.38 g) was added to a solution of (2-methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 4, step h) (0.62 g) and triethylamine (0.55 mL) in acetonitrile (5 mL) and the resulting mixture stirred for 16 h at 65° C. The solvent was evaporated in vacuo and the residue partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL). The aqueous phase was separated and extracted with ethyl acetate (2×25 mL). The organic phases were combined, washed with brine (25 mL), dried over sodium sulphate, filtered and evaporated in vacuo. Purification was by silica gel chromatography eluting with 47.5:47:5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient to give the subtitled compound as a yellow oil. Yield 0.48 g.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customthe residue partitioned between ethyl acetate (25 mL) and saturated sodium bicarbonate solution (25 mL)
  3. customThe aqueous phase was separated
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. washwashed with brine (25 mL)
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customPurification
  10. washeluting with 47.5:47:5:5 isohexane

Sources & evidence

ORD record
ord-9244e39660b548939b0c1d8bc658f4a1
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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