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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
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HRID 1526417 반응식
[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
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참가 물질

4

반응물 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

생성물 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)acetate수율 96.4%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-24cec14343d64fbe8a5082f793f26de6
출처 데이터셋
uspto-grants-2015_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09085581B2

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