Chlorosuccinimide → 2-(9-Chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

HRID 515705Notes

Reaction equation

HRID 515705 reaction equation
[CH:1]([O:4][C:5]1[CH:28]=[CH:27][C:8]([CH2:9][O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][CH:22]([CH2:23][C:24]([OH:26])=[O:25])[C:15]4=[CH:14][C:13]=3[CH:12]=2)=[CH:7][C:6]=1[C:29]([F:32])([F:31])[F:30])([CH3:3])[CH3:2].C1C(=O)N([Cl:40])C(=O)C1>C(Cl)Cl>[Cl:40][C:14]1[C:13]2[CH:12]=[C:11]([O:10][CH2:9][C:8]3[CH:27]=[CH:28][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[C:6]([C:29]([F:32])([F:30])[F:31])[CH:7]=3)[CH:19]=[CH:18][C:17]=2[N:16]2[CH2:20][CH2:21][CH:22]([CH2:23][C:24]([OH:26])=[O:25])[C:15]=12

Participants

4

Reactant 2

HCID 31398ChlorosuccinimideHCID 583296112-(7-(4-Isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Product 1

HCID 583296122-(9-Chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of the 1st enantiomer (described as the enantiomer isolated and having the retention time of 29.8 min per the conditions reported in Example 1.25) of 2-(7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic Acid (0.049 mmol) in DCM (0.5 mL) at 0° C. was added NCS (0.049 mmol). The reaction was stirred for 15 minutes. The mixture was diluted with DCM and washed with water (twice) and saturated sodium thiolsulfate (aq). The organics were dried over Na2SO4, filtered, and concentrated to give the title compound as a yellow solid. LCMS m/z=482.3 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29 (d, J=6.06 Hz, 6H), 2.24-2.35 (m, 1H), 2.51-2.59 (m, 1H), 2.77-2.87 (m, 1H), 2.94 (dd, J=16.36, 4.11 Hz, 1H), 3.62-3.74 (m, 1H), 3.96-4.05 (m, 1H), 4.11-4.19 (m, 1H), 4.74-4.83 (m, 1H), 5.10 (s, 2H), 6.86 (dd, J=8.78, 2.34 Hz, 1H), 6.96 (d, J=2.40 Hz, 1H), 7.28 (d, J=8.72 Hz, 1H), 7.31 (s, 1H), 7.65-7.72 (m, 2H), 12.35 (bs, 1H).

Workup

  1. customisolated
  2. customat 0° C.
  3. washwashed with water (twice) and saturated sodium thiolsulfate (aq)
  4. dry with materialThe organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-2510a97c2f70453ea451a9b6e8e5c1c5
Source dataset
uspto-grants-2015_08
Patent number
US09108969B2

Reaction notes

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