1-Hydroxybenzotriazole → Rac.-n-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester

HRID 1058411노트

반응식

HRID 1058411 반응식
C(N(C(C)C)CC)(C)C.[Cl:10][C:11]1[CH:19]=[C:18]([CH:20]([OH:30])[CH:21]=[CH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.[CH3:31][O:32][C:33](=[O:42])[CH:34]([P:36]([O:40][CH3:41])([O:38][CH3:39])=[O:37])[NH2:35].COC(=O)C(P(OC)(OC)=O)NC(OCC1C=CC=CC=1)=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.ON1C2C=CC=CC=2N=N1>CN(C)C=O.CO.C(OCC)(=O)C>[CH3:31][O:32][C:33](=[O:42])[CH:34]([P:36]([O:38][CH3:39])([O:40][CH3:41])=[O:37])[NH:35][C:13](=[O:15])[C:12]1[CH:16]=[CH:17][C:18]([CH:20]([OH:30])[CH:21]=[CH:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([OH:29])[CH:24]=2)=[CH:19][C:11]=1[Cl:10]

참가 물질

9

반응물 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetateHCID 11084793Methyl 2-amino-2-(dimethoxyphosphoryl)acetateHCID 700297522-Chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoic acid

생성물 1

HCID 74062779Rac.-n-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester수율 72%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 21584119Ethylacetate methanol용매

실험 절차

Diisopropylethylamine (0.48 mL, 2.8 mmol) was added to a solution of rac.-2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoic acid (Example 93; 225 mg, 0.69 mmol), rac.-2-(dimethoxyphosphinyl)glycine methyl ester (Example 125) freshly prepared from rac.-N-(benzyloxycarbonyl)-2-(dimethoxyphosphinyl)glycine methyl ester (331 mg, 1 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (284 mg, 0.75 mmol) and 1-hydroxybenzotriazole (102 mg, 0.76 mmol) in N,N-dimethylformamide (5 mL). The solution was stirred at room temperature for 17 h and then it was concentrated under high vacuum to remove N,N-dimethylformamide. Ethyl acetate (25 mL) was added and the resulting solution was washed in turn with 0.5N hydrochloric acid solution (10 mL), brine (10 mL), saturated sodium bicarbonate solution (10 mL) and brine (10 mL). Each of the aqueous layers was back-extracted in turn with ethyl acetate (10 mL). The combined organic layers were dried (MgSO4), filtered, evaporated and chromatographed over silica gel (50-100% ethyl acetate/hexanes, then 5% methanol/ethyl acetate) to furnish rac.-N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)prop-2-en-1-yl]benzoyl]-2-(dimethoxyphosphinyl)glycine methyl ester (240 mg, 72% yield) as an oil.

후처리

  1. concentrationit was concentrated under high vacuum
  2. customto remove N,N-dimethylformamide
  3. additionEthyl acetate (25 mL) was added
  4. washthe resulting solution was washed in turn with 0.5N hydrochloric acid solution (10 mL), brine (10 mL), saturated sodium bicarbonate solution (10 mL) and brine (10 mL)
  5. extractionEach of the aqueous layers was back-extracted in turn with ethyl acetate (10 mL)
  6. dry with materialThe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customchromatographed over silica gel (50-100% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-733e58a607544cac9d5732932ca3c97c
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06515124B2

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