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

HRID 446447Notes

Reaction equation

HRID 446447 reaction equation
[Cl:1][C:2]1[C:9]([CH2:10][CH2:11][OH:12])=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH2:13]([C:15]1[S:16][CH:17]=[C:18]([C:20]([N:22]2[CH2:27][C:26]3([CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[O:25][CH2:24][CH2:23]2)=[O:21])[N:19]=1)[CH3:14].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>C(Cl)Cl.C(N(CC)CC)C>[Cl:1][C:2]1[C:9]([CH2:10][CH2:11][OH:12])=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][N:30]1[CH2:31][CH2:32][C:26]2([O:25][CH2:24][CH2:23][N:22]([C:20]([C:18]3[N:19]=[C:15]([CH2:13][CH3:14])[S:16][CH:17]=3)=[O:21])[CH2:27]2)[CH2:28][CH2:29]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 579889292-Chloro-3-(2-hydroxyethyl)benzaldehydeHCID 58168456(2-Ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone

Product 1

HCID 58168486(9-(2-Chloro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-ethylthiazol-4-yl)methanoneYield 107%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 2-chloro-3-(2-hydroxyethyl)benzaldehyde (1.1 molar equivalents) in DCM (12 volumes) was added to (2-ethylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone ((limiting reagent) (step b). Triethylamine (2 molar equivalents) was added and the mixture was stirred for 1.15 hr. Sodium triacetoxyborohydride (2.5 molar equivalents) was added portion-wise over 15 minutes maintaining the temperature below 25° C. The reaction mixture was stirred at ambient temperature for 22.5 hr. Saturated aq. sodium bicarbonate solution (8 volumes) was added slowly and the mixture was stirred vigorously for 1 hr; the aqueous was separated and extracted with DCM (5.3 volumes). The combined organics were washed with 20% brine solution (5.3 volumes), dried over anhydrous sodium sulfate, filtered and evaporated to give a brown oil. Yield 107% of theoretical.

Workup

  1. temperaturemaintaining the temperature below 25° C
  2. stirringThe reaction mixture was stirred at ambient temperature for 22.5 hr
  3. stirringthe mixture was stirred vigorously for 1 hr
  4. customthe aqueous was separated
  5. extractionextracted with DCM (5.3 volumes)
  6. washThe combined organics were washed with 20% brine solution (5.3 volumes)
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customto give a brown oil

Sources & evidence

ORD record
ord-2dae08ab2c594b5e9ae58f334c20e904
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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