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

HRID 470953Notes

Reaction equation

HRID 470953 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][C:23]1[CH:32]=[CH:31][C:26]([O:27][CH2:28][CH:29]=O)=[CH:25][CH:24]=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][C:23]1[CH:32]=[CH:31][C:26]([O:27][CH2:28][CH2:29][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:25][CH:24]=1

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 544756782-(4-(Hydroxymethyl)phenoxy)acetaldehydeHCID 67291637(2-Methylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone hydrochloride

Product 1

HCID 46240301(9-(2-(4-(Hydroxymethyl)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) (0.38 g) was added to a solution of 2-(4-(hydroxymethyl)phenoxy)acetaldehyde (example 1, step h) (0.17 g) in NMP (10 mL) and acetic acid (0.06 mL). The resulting mixture was stirred for 30 min then cooled in an ice bath. Sodium triacetoxyborohydride (0.32 g) was then added and the reaction 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 (250 mL) and eluted with 3M ammonia in methanol solution (150 mL). The eluent was evaporated in vacuo and the residue purified by column chromatography eluting with 95:5 ethyl acetate:triethylamine to give the subtitled compound as a gum. Yield 0.32 g.

Workup

  1. temperaturethen cooled in an ice bath
  2. stirringstirred for 16 h
  3. washThe cartridge was washed with methanol (250 mL)
  4. washeluted with 3M ammonia in methanol solution (150 mL)
  5. customThe eluent was evaporated in vacuo
  6. customthe residue purified by column chromatography
  7. washeluting with 95:5 ethyl acetate

Sources & evidence

ORD record
ord-1fe01b4243f24ca7b02910407c4d5b4f
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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