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

HRID 471081Notes

Reaction equation

HRID 471081 reaction equation
Br[CH2:2][C:3]1[CH:4]=[CH:5][C:6]([F:12])=[C:7]([CH2:9][CH2:10][OH:11])[CH:8]=1.FC(F)(F)C(O)=O.[CH:20]([C:23]1[S:24][CH:25]=[C:26]([C:28]([N:30]2[CH2:35][C:34]3([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[O:33][CH2:32][CH2:31]2)=[O:29])[N:27]=1)([CH3:22])[CH3:21].C(N(CC)CC)C>C(#N)C>[F:12][C:6]1[CH:5]=[CH:4][C:3]([CH2:2][N:38]2[CH2:39][CH2:40][C:34]3([O:33][CH2:32][CH2:31][N:30]([C:28]([C:26]4[N:27]=[C:23]([CH:20]([CH3:21])[CH3:22])[S:24][CH:25]=4)=[O:29])[CH2:35]3)[CH2:36][CH2:37]2)=[CH:8][C:7]=1[CH2:9][CH2:10][OH:11]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 579890232-(5-(Bromomethyl)-2-fluorophenyl)ethanolHCID 66964182(2-Isopropylthiazol-4-yl)(1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)methanone trifluoroacetate

Product 1

HCID 57989065(9-(4-Fluoro-3-(2-hydroxyethyl)benzyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent3×

Procedure

2-(5-(Bromomethyl)-2-fluorophenyl)ethanol (example 47, step a) (0.16 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) (0.3 g) and triethylamine (0.3 mL) in acetonitrile (10 mL). The resulting mixture was stirred overnight, diluted with acetonitrile (20 mL) and applied to a SCX cartridge (10 g Varian, pre-wetted with acetonitrile (50 mL)). The cartridge was washed with acetonitrile (50 mL) and eluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL). The eluent was evaporated, azeotroped with toluene and purified by silica gel chromatography eluting with 77.5:17.5:5 isohexane:ethyl acetate:triethylamine to 95:5 ethyl acetate:triethylamine gradient. The fractions containing product were combined and evaporated to give to the subtitled compound as a yellow gum. Yield 0.22 g.

Workup

  1. washThe cartridge was washed with acetonitrile (50 mL)
  2. washeluted with 10% ‘880’ aqueous ammonia in acetonitrile solution (50 mL)
  3. customThe eluent was evaporated
  4. customazeotroped with toluene
  5. custompurified by silica gel chromatography
  6. washeluting with 77.5:17.5:5 isohexane
  7. additionThe fractions containing product
  8. customevaporated

Sources & evidence

ORD record
ord-c36c9c832c544072b0764ada472954d8
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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