Benzyltrimethylammonium hydroxide → tert-Butyl 3-(4-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanoate

HRID 446422Notes

Reaction equation

HRID 446422 reaction equation
[OH-:1].[CH2:2]([N+](C)(C)C)[C:3]1[CH:8]=CC=C[CH:4]=1.[OH:13][CH2:14][CH2:15][C:16]1[CH:44]=[CH:43][C:19]([CH2:20][CH2:21][N:22]2[CH2:42][CH2:41][C:25]3([O:30][CH2:29][CH2:28][N:27]([C:31]([C:33]4[N:34]=[C:35]([CH:38]([CH3:40])[CH3:39])[S:36][CH:37]=4)=[O:32])[CH2:26]3)[CH2:24][CH2:23]2)=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[CH:38]([C:35]1[S:36][CH:37]=[C:33]([C:31]([N:27]2[CH2:26][C:25]3([CH2:41][CH2:42][N:22]([CH2:21][CH2:20][C:19]4[CH:18]=[CH:17][C:16]([CH2:15][CH2:14][O:13][CH2:16][CH2:15][C:14]([O:13][C:3]([CH3:2])([CH3:4])[CH3:8])=[O:1])=[CH:44][CH:43]=4)[CH2:23][CH2:24]3)[O:30][CH2:29][CH2:28]2)=[O:32])[N:34]=1)([CH3:40])[CH3:39]

Participants

4

Reactant 2

HCID 66854Benzyltrimethylammonium hydroxideHCID 58168559(9-(4-(2-Hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone

Product 1

HCID 58168551tert-Butyl 3-(4-(2-(4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)ethyl)phenethoxy)propanoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

Benzyltrimethylammonium hydroxide (40% in methanol, 0.031 mL) was added to a solution of (9-(4-(2-hydroxyethyl)phenethyl)-1-oxa-4,9-diazaspiro[5.5]undecan-4-yl)(2-isopropylthiazol-4-yl)methanone [Example 1, step c] (0.62 g) in toluene (20 mL). The solvent was removed under reduced pressure and the residue azeotroped with toluene. The resultant liquid, which was just mobile with traces of toluene, was treated dropwise with tert-butyl acrylate (0.225 g). The reaction mixture was stirred at 20° C. for 18 hours. The mixture was purified by flash silica chromatography using 2% methanol in dichloromethane with 1% triethylamine as solvent. Fractions containing the product were evaporated to dryness to afford the subtitled compound. Yield 0.550 g.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue azeotroped with toluene
  3. additionwas treated dropwise with tert-butyl acrylate (0.225 g)
  4. customThe mixture was purified by flash silica chromatography
  5. additionFractions containing the product
  6. customwere evaporated to dryness

Sources & evidence

ORD record
ord-664bec0b7c0f4dba92d884009a5a763e
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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