Sodium triacetoxyborohydride → (9-(2-(2,3-Difluoro-4-(2-hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

HRID 1689399Notes

Reaction equation

HRID 1689399 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].[F:29][C:30]1[C:39]([F:40])=[C:38]([CH2:41][CH2:42][OH:43])[CH:37]=[CH:36][C:31]=1[O:32][CH2:33][CH:34]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1CCCC1=O.C(O)(=O)C>[F:29][C:30]1[C:39]([F:40])=[C:38]([CH2:41][CH2:42][OH:43])[CH:37]=[CH:36][C:31]=1[O:32][CH2:33][CH2:34][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

6

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetateHCID 866367532-(2,3-Difluoro-4-(2-hydroxyethyl)phenoxy)acetaldehyde

Product 1

HCID 57988904(9-(2-(2,3-Difluoro-4-(2-hydroxyethyl)phenoxy)ethyl)-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-pyrrolidoneSolvent

Procedure

(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate (example 22, step b) (0.5 g) was added to a solution of 2-(2,3-difluoro-4-(2-hydroxyethyl)phenoxy)acetaldehyde (example 77, step d) (0.31 g) in N-methyl-2-pyrrolidinone (10 mL) and acetic acid (0.07 mL). The resulting mixture was stirred for 30 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.38 g) was then added and the reaction was allowed to warm to RT and stirred overnight. The reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL). The aqueous phase was basified with saturated sodium hydrogen carbonate solution and the layers separated. The aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organic solutions were washed with water (100 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was purified by silica gel chromatography, eluting with 47.5:47.5:5 isohexane:ethylacetate:triethylamine to 5% triethylamine in ethyl acetate. The fractions containing product were combined and evaporated to give the subtitled compound as a clear gum. Yield 0.41 g.

Workup

  1. temperaturethen cooled in an ice bath
  2. stirringstirred overnight
  3. customThe reaction mixture was partitioned between ethyl acetate (100 mL) and water (100 mL)
  4. customthe layers separated
  5. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic solutions were washed with water (100 mL) and brine (100 mL)
  7. dry with materialdried over sodium sulphate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by silica gel chromatography
  11. washeluting with 47.5:47.5:5 isohexane
  12. additionThe fractions containing product
  13. customevaporated

Sources & evidence

ORD record
ord-c23615875da542de9bd6e4b63f8084e8
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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