Triethylamine → (3-(3-(2-Hydroxyethyl)benzyl)-7-oxa-3,10-diazaspiro[5.6]dodecan-10-yl)(2-methylthiazol-4-yl)methanone

HRID 471213Notes

Reaction equation

HRID 471213 reaction equation
FC(F)(F)C(O)=O.[CH3:8][C:9]1[S:10][CH:11]=[C:12]([C:14]([N:16]2[CH2:27][CH2:26][C:20]3([CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)[O:19][CH2:18][CH2:17]2)=[O:15])[N:13]=1.C(N(CC)CC)C.Br[CH2:36][C:37]1[CH:38]=[C:39]([CH2:43][CH2:44][OH:45])[CH:40]=[CH:41][CH:42]=1>C(#N)C>[OH:45][CH2:44][CH2:43][C:39]1[CH:38]=[C:37]([CH:42]=[CH:41][CH:40]=1)[CH2:36][N:23]1[CH2:24][CH2:25][C:20]2([CH2:26][CH2:27][N:16]([C:14]([C:12]3[N:13]=[C:9]([CH3:8])[S:10][CH:11]=3)=[O:15])[CH2:17][CH2:18][O:19]2)[CH2:21][CH2:22]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 18999576Benzeneethanol, 3-(bromomethyl)-HCID 67292347(2-Methylthiazol-4-yl)(7-oxa-3,10-diazaspiro[5.6]dodecan-10-yl)methanone trifluoroacetate

Product 1

HCID 57989079(3-(3-(2-Hydroxyethyl)benzyl)-7-oxa-3,10-diazaspiro[5.6]dodecan-10-yl)(2-methylthiazol-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
20 °C

Procedure

A solution of (2-methylthiazol-4-yl)(7-oxa-3,10-diazaspiro[5.6]dodecan-10-yl)methanone trifluoroacetate (example 89, step g) (0.21 g) in acetonitrile (15 mL) was treated with triethylamine (0.214 mL) followed by 2-(3-(bromomethyl)phenyl)ethanol (example 6, step a) (0.121 g). The reaction mixture was stirred for 3 hours at 20° C. The solvent was evaporated under reduced pressure and the residue was partitioned between DCM and saturated sodium bicarbonate solution. The aqueous layer was re-extracted twice with DCM and the combined organics were dried over sodium sulphate, filtered and the solvent removed under reduced pressure. The crude product was purified by flash silica chromatography using 6% methanol in dichloromethane with 1% triethylamine as solvent. Pure fractions were evaporated to dryness to afford the subtitled compound. Yield 0.21 g.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was partitioned between DCM and saturated sodium bicarbonate solution
  3. extractionThe aqueous layer was re-extracted twice with DCM
  4. dry with materialthe combined organics were dried over sodium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified by flash silica chromatography
  8. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-87a2a203bab94ca9b9cc84a061def4ae
Source dataset
uspto-grants-2014_01
Patent number
US08629271B2

Reaction notes

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