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

HRID 471137Notes

Reaction equation

HRID 471137 reaction equation
[OH:1][CH2:2][CH2:3][S:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH:8]=O.FC(F)(F)C(O)=O.[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([N:30]2[CH2:35][C:34]3([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[O:33][CH2:32][CH2:31]2)=[O:29])[N:27]=1)([CH3:22])[CH3:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>CN1CCCC1=O.O.C(O)(=O)C>[OH:1][CH2:2][CH2:3][S:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][CH:12]=1)[CH2:8][N:38]1[CH2:39][CH2:40][C:34]2([O:33][CH2:32][CH2:31][N:30]([C:28]([C:26]3[N:27]=[C:23]([CH:20]([CH3:21])[CH3:22])[S:24][CH:25]=3)=[O:29])[CH2:35]2)[CH2:36][CH2:37]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579891823-(2-Hydroxyethylthio)benzaldehydeHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989280(9-(3-(2-Hydroxyethylthio)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 3

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

Procedure

3-(2-Hydroxyethylthio)benzaldehyde (example 65, step c) (0.16 g) was added to a solution of (2-isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.25 g) and acetic acid (0.046 mL) in N-methyl-2-pyrrolidinone (5 mL) and the resulting mixture was stirred for 1 h and cooled in an ice bath. Sodium triacetoxyborohydride (0.26 g) was then added and the mixture allowed to warm to RT and stirred overnight. The reaction was poured into a mixture of sodium bicarbonate solution (20 mL) and water (80 mL). The aqueous phase was extracted with ether (3×100 mL). The combined organic solutions were washed with brine (100 mL), dried over sodium sulphate, filtered and evaporated. The crude product was purified by silica gel chromatography eluting with 95:5 ethyl acetate:triethylamine. The fractions containing product were combined and evaporated to give the subtitled compound as a yellow oil. Yield 0.22 g.

Workup

  1. temperaturecooled in an ice bath
  2. stirringstirred overnight
  3. extractionThe aqueous phase was extracted with ether (3×100 mL)
  4. washThe combined organic solutions were washed with brine (100 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 95:5 ethyl acetate
  10. additionThe fractions containing product
  11. customevaporated

Sources & evidence

ORD record
ord-43d9538df9a44f2c99e50440a4cdbd74
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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