Trifluoroacetic acid → N-{(S)-3-[3-(4-fluorophenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-3,4,5-trimethoxy-benzamide

HRID 1182126Notes

Reaction equation

HRID 1182126 reaction equation
C([O:5][CH2:6][C@@H:7]([NH:22][C:23](=[O:36])[C:24]1[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26]([O:34][CH3:35])[CH:25]=1)[CH2:8][CH2:9][N:10]1[CH2:13][CH:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)[CH2:11]1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[F:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][CH:12]2[CH2:11][N:10]([CH2:9][CH2:8][C@H:7]([NH:22][C:23](=[O:36])[C:24]3[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26]([O:34][CH3:35])[CH:25]=3)[CH2:6][OH:5])[CH2:13]2)=[CH:16][CH:17]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 10289176N-{(S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propyl}-3,4,5-trimethoxy-benzamide

Product 1

HCID 10310458N-{(S)-3-[3-(4-fluorophenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-3,4,5-trimethoxy-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-{(S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propyl}-3,4,5-trimethoxy-benzamide (Example 1, 0.066 g, 0.130 mmol) in dichloromethane (2 ml) is treated with trifluoroacetic acid (0.11 ml, 0.65 mmol) and the reaction mixture stirred for 20 hours. The solvent is evaporated and the residue partitioned between ethylacetate and saturated aqueous NaHCO3. The ethylacetate phase is washed with brine, dried over magnesium sulphate and evaporated. The crude product is purified by flash silica chromatography (elution 100% ethylacetate then 5:95 methanol/dichloromethane) to afford N-{(S)-3-[3-(4-fluorophenoxy)-azetidin-1-yl]-1-hydroxymethyl-propyl}-3,4,5-trimethoxy-benzamide [MH]+ 449.1.

Workup

  1. customThe solvent is evaporated
  2. customthe residue partitioned between ethylacetate and saturated aqueous NaHCO3
  3. washThe ethylacetate phase is washed with brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe crude product is purified by flash silica chromatography (
  7. washelution 100% ethylacetate

Sources & evidence

ORD record
ord-6a2481ef0ce647b6982b3063347f2b67
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

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