3,4,5-Trimethoxybenzoic Acid → N-{(S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propyl}-3,4,5-trimethoxy-benzamide

HRID 1182125Notes

Reaction equation

HRID 1182125 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:14][CH3:15])[C:11]=1[O:12][CH3:13])[C:6]([OH:8])=O.C(N(C(C)C)CC)(C)C.N1(OC(=[N+](C)C)N(C)C)C2C=CC=CC=2N=N1.[B-](F)(F)(F)F.CCCC[P+](C1SC(C(OC)=O)=C(C(OC)=O)S1)(CCCC)CCCC.[C:73]([O:77][CH2:78][C@@H:79]([NH2:94])[CH2:80][CH2:81][N:82]1[CH2:85][CH:84]([O:86][C:87]2[CH:92]=[CH:91][C:90]([F:93])=[CH:89][CH:88]=2)[CH2:83]1)([CH3:76])([CH3:75])[CH3:74]>CN(C)C=O>[C:73]([O:77][CH2:78][C@@H:79]([NH:94][C:6](=[O:8])[C:5]1[CH:9]=[C:10]([O:14][CH3:15])[C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=1)[CH2:80][CH2:81][N:82]1[CH2:83][CH:84]([O:86][C:87]2[CH:88]=[CH:89][C:90]([F:93])=[CH:91][CH:92]=2)[CH2:85]1)([CH3:76])([CH3:74])[CH3:75]

Participants

7

Reactant 5

HCID 83573,4,5-Trimethoxybenzoic AcidHCID 81531DiisopropylethylamineHCID 130500O-benzotriazol-1-yl-tetramethyluroniumHCID 498382(4,5-Bis-methoxycarbonyl-[1,3]dithiol-2-yl)-tributyl-phosphoniumHCID 69411039(S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propylamine

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3,4,5-trimethoxy-benzoic acid (0.246 g, 1.16 mmol) and diisopropylethylamine (0.62 ml, 3.47 mmol) in dry dimethylformamide (10 ml) is treated with [(benzotriazol-1-yloxy)-dimethylamino methylene]-dimethyl-ammonium; tetrafluoro borate (0.32 g, 1.0 mmol). The reaction mixture is stirred at ambient temperature for 5 minutes, then (S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propylamine (0.968 mmol) is added and the reaction mixture stirred for 20 hours. The dimethylformamide is evaporated and the residue partitioned between ethylacetate and saturated aqueous NaHCO3. The ethylacetate phase is washed with brine, dried over MgSO4 and evaporated. The crude product is purified by flash silica chromatography (elution 50% ethylacetate/hexane to 100% ethylacetate) to afford N-{(S)-1-tert-butoxymethyl-3-[3-(4-fluoro-phenoxy)-azetidin-1-yl]-propyl}-3,4,5-trimethoxy-benzamide [MH]+ 505.3.

Workup

  1. stirringthe reaction mixture stirred for 20 hours
  2. customThe dimethylformamide is evaporated
  3. customthe residue partitioned between ethylacetate and saturated aqueous NaHCO3
  4. washThe ethylacetate phase is washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe crude product is purified by flash silica chromatography (elution 50% ethylacetate/hexane to 100% ethylacetate)

Sources & evidence

ORD record
ord-d08c81c44dd54631bf1a2672cd96e0f7
Source dataset
uspto-grants-2007_10
Patent number
US07288537B2

Reaction notes

Loading…