Sodium triacetoxyborohydride → (9-(2-(4-(2-Hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

HRID 1689190Notes

Reaction equation

HRID 1689190 reaction equation
Cl.[CH3:2][C:3]1[S:4][CH:5]=[C:6]([C:8]([N:10]2[CH2:15][C:14]3([CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)[O:13][CH2:12][CH2:11]2)=[O:9])[N:7]=1.[OH:21][CH2:22][CH2:23][C:24]1[CH:33]=[CH:32][C:27]([O:28][CH2:29][CH:30]=O)=[CH:26][CH:25]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.CO>[OH:21][CH2:22][CH2:23][C:24]1[CH:33]=[CH:32][C:27]([O:28][CH2:29][CH2:30][N:18]2[CH2:19][CH2:20][C:14]3([O:13][CH2:12][CH2:11][N:10]([C:8]([C:6]4[N:7]=[C:3]([CH3:2])[S:4][CH:5]=4)=[O:9])[CH2:15]3)[CH2:16][CH2:17]2)=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 545162782-(4-(2-Hydroxyethyl)phenoxy)acetaldehydeHCID 67291637(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride

Product 1

HCID 57988908(9-(2-(4-(2-Hydroxyethyl)phenoxy)ethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-methylthiazol-4-yl)methanone

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride (example 1, step f) (0.63 g) was added to a solution of 2-(4-(2-hydroxyethyl)phenoxy)acetaldehyde (example 3, step b) (0.541 g) in a mixture of NMP (10 mL) and acetic acid (0.11 mL). The resulting mixture was stirred at room temperature for 30 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.64 g) was then added and the reaction was allowed to warm to room temperature and stirred for 16 h. The reaction was diluted with methanol (30 mL) and applied to a SCX cartridge pre-wetted with methanol. The cartridge was washed with methanol (100 mL) and eluted with 3M ammonia in methanol solution (100 mL). The eluent was evaporated in vacuo and the residue purified by silica gel chromatography, eluting with 95:5 ethyl acetate:triethylamine to give the subtitled compound as a brown oil. Yield 0.74 g.

Workup

  1. temperaturethen cooled in an ice bath
  2. temperatureto warm to room temperature
  3. stirringstirred for 16 h
  4. washThe cartridge was washed with methanol (100 mL)
  5. washeluted with 3M ammonia in methanol solution (100 mL)
  6. customThe eluent was evaporated in vacuo
  7. customthe residue purified by silica gel chromatography
  8. washeluting with 95:5 ethyl acetate

Sources & evidence

ORD record
ord-eb0d4eb9e228495e8a71a519f9a52fef
Source dataset
uspto-grants-2012_04
Patent number
US08148373B2

Reaction notes

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