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

HRID 1689435Notes

Reaction equation

HRID 1689435 reaction equation
[Si]([O:8][CH2:9][CH2:10][CH2:11][C:12]1[C:13]([F:20])=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH:15]=O)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O.[CH:28]([C:31]1[S:32][CH:33]=[C:34]([C:36]([N:38]2[CH2:43][C:42]3([CH2:48][CH2:47][NH:46][CH2:45][CH2:44]3)[O:41][CH2:40][CH2:39]2)=[O:37])[N:35]=1)([CH3:30])[CH3:29].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>CN1CCCC1=O.O.C(O)(=O)C>[F:20][C:13]1[C:12]([CH2:11][CH2:10][CH2:9][OH:8])=[CH:19][CH:18]=[CH:17][C:14]=1[CH2:15][N:46]1[CH2:47][CH2:48][C:42]2([O:41][CH2:40][CH2:39][N:38]([C:36]([C:34]3[N:35]=[C:31]([CH:28]([CH3:29])[CH3:30])[S:32][CH:33]=3)=[O:37])[CH2:43]2)[CH2:44][CH2:45]1

Participants

8

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 57989086HCID 57989086, compoundHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57988960(9-(2-Fluoro-3-(3-hydroxypropyl)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-(3-(tert-Butyldimethylsilyloxy)propyl)-2-fluorobenzaldehyde (example 88, step c) (0.15 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) (0.19 g) and acetic acid (0.03 mL) in N-methyl-2-pyrrolidinone (10 mL). The resulting mixture was stirred for 15 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.16 g) was then added and the mixture stirred overnight. The reaction was poured into a mixture of saturated sodium hydrogen carbonate solution (20 mL) and water (100 mL). The aqueous was extracted with ethyl acetate (3×100 mL). The combined organics were washed with water (50 mL) and brine (100 mL), dried over sodium sulphate, filtered and evaporated. The residue was redissolved in THF (10 mL) and a solution of TBAF (1M in THF, 1.52 mL) was added. The resulting mixture was stirred for 2 h and the solvent evaporated. The residue was purified by column chromatography eluting with 4:1 isohexane:ethyl acetate+5% triethylamine to ethyl acetate+5% triethylamine gradient. The fractions containing product were combined and evaporated to give the subtitled compound as a clear oil. Yield 0.22 g.

Workup

  1. temperaturethen cooled in an ice bath
  2. stirringthe mixture stirred overnight
  3. extractionThe aqueous was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organics were washed with water (50 mL) and brine (100 mL)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. customevaporated
  8. dissolutionThe residue was redissolved in THF (10 mL)
  9. additiona solution of TBAF (1M in THF, 1.52 mL) was added
  10. stirringThe resulting mixture was stirred for 2 h
  11. customthe solvent evaporated
  12. customThe residue was purified by column chromatography
  13. washeluting with 4:1 isohexane
  14. additionThe fractions containing product
  15. customevaporated

Sources & evidence

ORD record
ord-70e69aa136bb452381ebe17baa30db5d
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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