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Chlorosuccinimide → (R)-ethyl 2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

HRID 1526417
ノート
印刷プレビュー

反応式

HRID 1526417 の反応式
[CH:1]([O:4][C:5]1[CH:30]=[CH:29][C:8]([CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][C@H:22]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:15]4=[CH:14][C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:31]([F:34])([F:33])[F:32])([CH3:3])[CH3:2].C1C(=O)N([Cl:42])C(=O)C1>C(Cl)Cl>[Cl:42][C:14]1[C:13]2[CH:12]=[C:11]([O:10][CH2:9][C:8]3[CH:29]=[CH:30][C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[C:6]([C:31]([F:34])([F:32])[F:33])[CH:7]=3)[CH:19]=[CH:18][C:17]=2[N:16]2[CH2:20][CH2:21][C@H:22]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:15]=12
参加物実験手順後処理出典と根拠反応ノート

参加物

4

反応物 2

HCID 31398ChlorosuccinimideHCID 71141942(R)-ethyl 2-(7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate

生成物 1

HCID 68240766(R)-ethyl 2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate収率 96.4%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of (R)-ethyl 2-(7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (52.8 g, 111 mmol) in DCM (350 mL) at −5° C. (ice-salt bath) was added a solution of NCS (14.8 g, 111 mmol) in DCM (350 mL) slowly over 20 min via addition funnel. After stirring for 0.5 h the mixture was washed w/sat. aq. sodium thiosulfate (300 mL). The organics were concentrated to about 300 mL and filtered using a column (60 cm×80 cm) containing sodium sulfate (top layer), sand (middle layer), and silica gel (bottom) using DCM as the eluant. The filtrate was concentrated to give (R)-ethyl 2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate (54.6 g, 107 mmol, 96% yield) as a white/mildly yellow solid. Exact mass calculated for C26H27ClF3NO4: 509.2, found: LCMS m/z=510.3, [M+H+]; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (t, J=7.1 Hz, 3 H), 1.37 (d, J=6.1 Hz, 6 H), 2.34 (m, 1 H), 2.52 (dd, J1=16.3, J2=10.2 Hz, 1 H), 2.93 (m, 1 H), 3.22 (dd, J1=16.3, J2=4.0 Hz, 1 H), 3.81 (m, 1 H), 4.00 (m, 1 H), 4.12 (m, 1 H), 4.20 (qd, J1=7.1, J2=1.7 Hz, 2 H), 4.65 (sep, J=6.1 Hz, 1 H), 5.04 (s, 2 H), 6.89 (dd, J1=8.8, J2=2.4 Hz, 1 H), 7.01 (d, J=8.6 Hz, 1 H), 7.06 (d, J=2.4 Hz, 1 H), 7.12 (d, J=8.8 Hz, 1 H), 7.56 (dd, J1=8.5, J2=1.9 Hz, 1 H), 7.67 (d, J=1.9 Hz, 1 H).

後処理

  1. additionvia addition funnel
  2. washwas washed w/sat
  3. concentrationThe organics were concentrated to about 300 mL
  4. filtrationfiltered
  5. additioncontaining sodium sulfate (top layer), sand (middle layer), and silica gel (bottom)
  6. concentrationThe filtrate was concentrated

出典と根拠

ORDレコード
ord-24cec14343d64fbe8a5082f793f26de6
出典データセット
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09085581B2

反応ノート

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