Trifluoroacetic acid → 3-(2-Fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid

HRID 1255309Notes

Reaction equation

HRID 1255309 reaction equation
C(O)(C(F)(F)F)=O.[F:8][C:9]1[C:26]([CH2:27][N:28]2[CH2:48][CH2:47][C:31]3([O:36][CH2:35][CH2:34][N:33]([C:37]([C:39]4[N:40]=[C:41]([CH:44]([CH3:46])[CH3:45])[S:42][CH:43]=4)=[O:38])[CH2:32]3)[CH2:30][CH2:29]2)=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][CH2:12][O:13][CH2:14][CH2:15][C:16]([O:18]C(C)(C)C)=[O:17]>C(Cl)Cl>[F:8][C:9]1[C:26]([CH2:27][N:28]2[CH2:29][CH2:30][C:31]3([O:36][CH2:35][CH2:34][N:33]([C:37]([C:39]4[N:40]=[C:41]([CH:44]([CH3:45])[CH3:46])[S:42][CH:43]=4)=[O:38])[CH2:32]3)[CH2:47][CH2:48]2)=[CH:25][CH:24]=[CH:23][C:10]=1[CH2:11][CH2:12][O:13][CH2:14][CH2:15][C:16]([OH:18])=[O:17]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58168472tert-Butyl 3-(2-fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoate

Product 1

HCID 669637983-(2-Fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (10 mL) was cautiously added to a solution of tert-butyl 3-(2-fluoro-3-((4-(2-isopropylthiazole-4-carbonyl)-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)methyl)phenethoxy)propanoate [Example 7, step c] (3.95 g) in DCM (40 mL). The resulting mixture was stirred for 2 h. The solvent was evaporated and the residue azeotroped twice with acetonitrile. The residue was dissolved in freshly distilled 2-methyltetrahydrofuran (100 mL) and washed 3 times with a mixture of brine and saturated sodium bicarbonate solution (10:1, 100 mL). The organic phase was dried over sodium sulphate, filtered and evaporated. The residue was azeotroped 3 times with isohexane to give the subtitled compound as a white foam. Yield 2.92 g.

Workup

  1. customThe solvent was evaporated
  2. customthe residue azeotroped twice with acetonitrile
  3. dissolutionThe residue was dissolved in freshly distilled 2-methyltetrahydrofuran (100 mL)
  4. washwashed 3 times
  5. additionwith a mixture of brine and saturated sodium bicarbonate solution (10:1, 100 mL)
  6. dry with materialThe organic phase was dried over sodium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was azeotroped 3 times with isohexane

Sources & evidence

ORD record
ord-e7c419c5bf1f42d09003d4dbe3f7a046
Source dataset
uspto-grants-2013_06
Patent number
US08455483B2

Reaction notes

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