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

HRID 1058411ノート

反応式

HRID 1058411 の反応式
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]

参加物

9

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 21584119Ethylacetate methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-733e58a607544cac9d5732932ca3c97c
出典データセット
uspto-grants-2003_02
特許番号
US06515124B2

反応ノート

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