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Acetic Acid → 3-[(2-Benzyloxy-ethyl)-(2-chloro-5-methoxy-phenyl)-amino]-2-hydroxy-cyclohex-1-ene carboxylic acid ethyl ester

HRID 628699
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HRID 628699 반응식
[CH2:1]([O:8][CH2:9][CH2:10][NH:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=1[Cl:20])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH2:31]([O:33][C:34]([C:36]1[CH2:41][CH2:40][CH2:39][CH:38](Br)[C:37]=1[OH:43])=[O:35])[CH3:32].C(O)(=O)C>C1COCC1.C1(C)C=CC=CC=1>[CH2:31]([O:33][C:34]([C:36]1[CH2:41][CH2:40][CH2:39][CH:38]([N:11]([CH2:10][CH2:9][O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C:12]2[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[CH:14][C:13]=2[Cl:20])[C:37]=1[OH:43])=[O:35])[CH3:32]
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참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 3251421Potassium bis(trimethylsilyl)amideHCID 590519613-Bromo-2-hydroxy-cyclohex-1-enecarboxylic acid ethyl esterHCID 66679111(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl)amine

생성물 1

HCID 666798493-[(2-Benzyloxy-ethyl)-(2-chloro-5-methoxy-phenyl)-amino]-2-hydroxy-cyclohex-1-ene carboxylic acid ethyl ester수율 104.9%

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매2회

실험 절차

(2-Benzyloxy-ethyl)-(2-chloro-5-methoxyphenyl) amine (3) (10.0 g, 34.2 mmol) was stirred in dry THF (100 mL) at −40° C. under nitrogen and potassium bis(trimethylsilyl) amide (143.0 mL of a 0.5 M solution in toluene, 72.0 mmol) was added over 30 min. 3-bromo-2-hydroxycyclohex-1-enecarboxylic acid ethyl ester (4) (8.5 g, 34.2 mmol) in dry THF (10 mL) was then added and allowed to warm to RT over a period of 1.5 h. Acetic acid (10.0 g, 166 mmol, 10.0 mL) was added and concentrated in vacuo to remove the THF. Ethyl acetate (200 mL) and 10% aqueous potassium carbonate (100 mL) was added and the mixture vigorously shaken. The ethyl acetate solution was separated, dried over magnesium sulfate and concentrated in vacuo to afford 16.5 g (quantitative) of 3[(2-Benzyloxy-ethyl)-(2-chloro-5-methoxy-phenyl)-amino]-2-hydroxy-cyclohex-1-ene carboxylic acid ethyl ester (5) as a gum which was used crude in the next step. HPLC (Gemini 150×4.6 mm, 50-95% methanol/water over 20 min) of crude reaction mixture, 18.9 min (38%), 19.2 min (25%), 23.1 min (28%). One component of the reaction was isolated 13C NMR (75 MHz, CDCl3) δC 14.3, 20.6, 21.8, 26.4, 38.6, 43.0, 55.8, 60.5, 68.7, 73.3, 93.4, 106.3, 108.2, 119.3, 121.5, 127.5, 127.6, 128.3, 135.7, 137.0, 137.9, 155.7, and 175.0.

후처리

  1. concentrationconcentrated in vacuo
  2. customto remove the THF
  3. additionEthyl acetate (200 mL) and 10% aqueous potassium carbonate (100 mL) was added
  4. customThe ethyl acetate solution was separated
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-27b3d2212b004187b405d0cbe8d0b60e
출처 데이터셋
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09314541B2

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