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 1182125노트

반응식

HRID 1182125 반응식
[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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-d08c81c44dd54631bf1a2672cd96e0f7
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07288537B2

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