1-Ethynylcyclohexanol → 2,2,2-trifluoro-N-(3-hydroxy-3-(4-((1-hydroxycyclohexyl)ethynyl)thiophen-2-yl)propyl)acetamide

HRID 63305

반응식

HRID 63305 반응식
Br[C:2]1[CH:3]=[C:4]([CH:7]([OH:17])[CH2:8][CH2:9][NH:10][C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[S:5][CH:6]=1.[C:18]([C:20]1([OH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1)#[CH:19]>CCN(CC)CC.[Cu]I>[F:13][C:12]([F:15])([F:14])[C:11]([NH:10][CH2:9][CH2:8][CH:7]([OH:17])[C:4]1[S:5][CH:6]=[C:2]([C:19]#[C:18][C:20]2([OH:26])[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)[CH:3]=1)=[O:16]

참가 물질

5

반응물 2

HCID 65251-EthynylcyclohexanolHCID 86694591N-(3-(4-bromothiophen-2-yl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide

생성물 1

HCID 866945922,2,2-trifluoro-N-(3-hydroxy-3-(4-((1-hydroxycyclohexyl)ethynyl)thiophen-2-yl)propyl)acetamide

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8471Triethylamine용매

실험 절차

Solution of N-(3-(4-bromothiophen-2-yl)-3-hydroxypropyl)-2,2,2-trifluoroacetamide (0.77 g, 2.32 mmol) and 1-ethynylcyclohexanol (0.48 g, 3.87 mmol) in Et3N (10 mL) was degassed by bubbling Ar for 5 min. CuI (0.0482 g, 0.253 mmol) and PdCl2(Ph3P)2 (0.0874 g, 0.125 mmol) were added to the reaction mixture and degassed by alternating vacuum/Ar once. The reaction mixture was stirred at +80° C. overnight, partitioned between EtOAc and aqueous NH4Cl (25%). Aqueous layer was additionally extracted with EtOAc and combined organic layers were washed with brine. Concentration under reduced pressure followed by flash chromatography purification (10%-75% EtOAc—hexanes gradient) gave 2,2,2-trifluoro-N-(3-hydroxy-3-(4-((1-hydroxycyclohexyl)ethynyl)thiophen-2-yl)propyl)acetamide as a light yellow oil. Yield (0.52 g, 60%); 1H NMR (400 MHz, DMSO-d6) δ 9.37 (br.s, 1H), 7.52 (d, J=1.3 Hz, 1H), 6.92 (d, J=1.3 Hz, 1H), 5.78 (d, J=4.7 Hz, 1H), 5.34 (s, 1H), 4.74-4.81 (m, 1H), 3.20-3.30 (m, 2H), 1.84-1.91 (m, 2H), 1.74-1.84 (m, 2H), 1.56-1.65 (m, 2H), 1.38-1.56 (m, 6H).

후처리

  1. customby bubbling Ar for 5 min
  2. customdegassed
  3. custompartitioned between EtOAc and aqueous NH4Cl (25%)
  4. extractionAqueous layer was additionally extracted with EtOAc
  5. washwere washed with brine
  6. concentrationConcentration under reduced pressure
  7. customfollowed by flash chromatography purification (10%-75% EtOAc—hexanes gradient)

출처 및 근거

ORD 기록
ord-fec88e3f4ddf46e38ceb32bc426daf47
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447078B2

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