Diisopropylethylamine → Methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate

HRID 541372노트

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HRID 541372 반응식
[CH:1]1([C:4]2[C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:7]([C:8]([OH:10])=O)=[C:6]([CH2:17][CH3:18])[CH:5]=2)[CH2:3][CH2:2]1.Cl.[F:20][C:21]1([C:27]2[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=2)[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[C:31]([C:30]1[CH:29]=[CH:28][C:27]([C:21]2([F:20])[CH2:26][CH2:25][N:24]([C:8]([C:7]3[C:6]([CH2:17][CH3:18])=[CH:5][C:4]([CH:1]4[CH2:2][CH2:3]4)=[C:12]([CH:11]=3)[C:13]([O:15][CH3:16])=[O:14])=[O:10])[CH2:23][CH2:22]2)=[CH:34][CH:33]=1)#[N:32]

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 682881524-Cyclopropyl-2-ethyl-5-(methoxycarbonyl)benzoic acid2회HCID 682888554-(4-Fluoropiperidin-4-yl)benzonitrile hydrochloride2회

생성물 1

HCID 68288315Methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
20 °C

실험 절차

To a solution of 4-cyclopropyl-2-ethyl-5-(methoxycarbonyl)benzoic acid (compound 226.6, 150 mg, 0.600 mmol, 1.00 equiv) in N,N-dimethylformamide (15 mL) were added 4-(4-fluoropiperidin-4-yl)benzonitrile hydrochloride (compound 11.2, 150 mg, 0.620 mmol, 1.00 equiv), DIPEA (450 mg, 3.49 mmol, 6.00 equiv), and HBTU (300 mg, 0.790 mmol, 1.30 equiv). The resulting solution was stirred for 4 h at 20° C., then quenched by the addition of 20 mL of brine. The resulting mixture was extracted with 4×30 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified via silica gel column with ethyl acetate/petroleum ether (1:3) as eluent. This resulted in 0.200 g (76%) of methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate as a light yellow solid.

후처리

  1. customquenched by the addition of 20 mL of brine
  2. extractionThe resulting mixture was extracted with 4×30 mL of ethyl acetate
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel column with ethyl acetate/petroleum ether (1:3) as eluent
  6. customThis resulted in 0.200 g (76%) of methyl 5-(4-(4-cyanophenyl)-4-fluoropiperidine-1-carbonyl)-2-cyclopropyl-4-ethylbenzoate as a light yellow solid

출처 및 근거

ORD 기록
ord-f67335224c804b9eb9ba54a90ca90655
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08871790B2

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