Toluene → 3-(2-Chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid

HRID 446449Notes

Reaction equation

HRID 446449 reaction equation
[Cl:1][C:2]1[C:19]([CH2:20][N:21]2[CH2:40][CH2:39][C:24]3([O:29][CH2:28][CH2:27][N:26]([C:30]([C:32]4[N:33]=[C:34]([CH2:37][CH3:38])[S:35][CH:36]=4)=[O:31])[CH2:25]3)[CH2:23][CH2:22]2)=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][CH2:5][O:6][CH2:7][CH2:8][C:9]([O:11]C(C)(C)C)=[O:10].FC(F)(F)C(O)=O.C1(C)C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[C:19]([CH2:20][N:21]2[CH2:22][CH2:23][C:24]3([O:29][CH2:28][CH2:27][N:26]([C:30]([C:32]4[N:33]=[C:34]([CH2:37][CH3:38])[S:35][CH:36]=4)=[O:31])[CH2:25]3)[CH2:39][CH2:40]2)=[CH:18][CH:17]=[CH:16][C:3]=1[CH2:4][CH2:5][O:6][CH2:7][CH2:8][C:9]([OH:11])=[O:10]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6422Trifluoroacetic acid2×HCID 58168518Tert-butyl 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoate

Product 1

HCID 581684923-(2-Chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acidYield 200%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of tert-butyl 3-(2-chloro-3-((4-(2-ethylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoate (limiting reagent) (step d) in DCM (2.8 volumes) was cooled to 5° C. Trifluoroacetic acid (10 molar equivalents) was added over 20 min (exotherm to 15° C.). The reaction mixture was warmed to ambient and stirred for 18 hr, Toluene (3 volumes) was added and the mixture was evaporated. The resulting gum was triturated with toluene (2×1.5 volumes) and evaporated to give a brown gum. Yield: 200% of theoretical. (carried through crude—NMR assay shows ˜45% by weight purity with remaining weight due to TFA trapped in the gum)

Workup

  1. temperatureThe reaction mixture was warmed to ambient and
  2. customthe mixture was evaporated
  3. customThe resulting gum was triturated with toluene (2×1.5 volumes)
  4. customevaporated
  5. customto give a brown gum

Sources & evidence

ORD record
ord-2cdd0fe0a6ee4216a73c6fe418cf8bdc
Source dataset
uspto-grants-2013_07
Patent number
US08476265B2

Reaction notes

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