Triethylamine → 5-Methyl-3-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionyl oxymethyl)-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid methyl ester

HRID 919009

반응식

HRID 919009 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:16]=[CH:15][C:8]2[O:9][CH2:10][CH:11]([CH2:13][OH:14])[O:12][C:7]=2[C:6]=1[CH3:17])=[O:4].C(N(CC)CC)C.[CH3:25][O:26][C@:27]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)([C:31]([F:34])([F:33])[F:32])[C:28](Cl)=[O:29]>C(Cl)Cl>[CH3:1][O:2][C:3]([C:5]1[CH:16]=[CH:15][C:8]2[O:9][CH2:10][CH:11]([CH2:13][O:14][C:28](=[O:29])[C:27]([O:26][CH3:25])([C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:31]([F:33])([F:34])[F:32])[O:12][C:7]=2[C:6]=1[CH3:17])=[O:4]

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 3080792(-)-alpha-Methoxy-alpha-(trifluoromethyl)phenylacetyl chloride2회HCID 687788313-Hydroxymethyl-5-methyl-2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid methyl ester

생성물 1

HCID 687829545-Methyl-3-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionyl oxymethyl)-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid methyl ester

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

To a round bottom flask equipped with magnetic stirring and a nitrogen inlet was added 3-hydroxymethyl-5-methyl-2,3-dihydrobenzo[1,4]dioxine-6-carboxylic acid methyl ester (0.10 g, 0.44 mmol) and dry methylene chloride (1.5 mL). The mixture was cooled in an ice bath and triethylamine (0.12 mL, 0.87 mmol) was added followed by (R)-(−)-α-methoxy-α-trifluoromethylphenylacetyl chloride (0.09 mL, 0.48 mmol). The mixture was stirred for 2 hours at which point TLC showed the reaction to be incomplete. More (R)-(−)-α-methoxy-α-trifluoromethylphenylacetyl chloride (0.09 mL, 0.48 mmol) was added and the reaction was allowed to stir 1 hour at room temperature. The mixture was diluted with methylene chloride, washed once with 1N HCl, once with saturated sodium bicarbonate, dried over magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel eluting with methylene chloride to give a clear oil, 5-methyl 3-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionyloxymethyl)-2,3-dihydro-benzo[1,4]dioxine-6-carboxylic acid methyl ester, for which a yield was not determined. 1H-NMR (300 MHz, CD3COCD3) δ (ppm): 2.38 (s, 3H), 3.58 (s, 3H), 3.81 (s, 3H), 4.10 (m, 1H), 4.48 (dd, 1H), 4.65 (m, 2H), 4.86 (m, 1H) 6.78 (d, 1H) 7.47 (m, 5H), 7.60 (d, 1H); 19F-NMR (300 MHz, CD3COCD3) δ (ppm): −72.89 (s); both 1H- and 19F-NMR indicate the presence of only one stereo- and regioisomer; TLC: Rf=0.62 (1:1 ethyl acetate/hexane).

후처리

  1. customTo a round bottom flask equipped
  2. temperatureThe mixture was cooled in an ice bath
  3. stirringThe mixture was stirred for 2 hours at which point TLC
  4. customthe reaction
  5. stirringto stir 1 hour at room temperature
  6. washwashed once with 1N HCl, once with saturated sodium bicarbonate
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was chromatographed on silica gel eluting with methylene chloride

출처 및 근거

ORD 기록
ord-dcb5ab3c4b134c519dd93c070be34cfd
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09272986B2

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