1-Chloro-4-iodobutane → 6-Chloro-2-(4-(2,2,2-trifluoroethoxy)phenyl)hexanoic acid
Reaction equation
[F:1][C:2]([F:16])([F:15])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:27][CH2:28][CH2:29][CH2:30][CH2:31]I>>[Cl:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:11]([C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:3][C:2]([F:15])([F:16])[F:1])=[CH:10][CH:9]=1)[C:12]([OH:14])=[O:13]Participants
4
Procedure
Step AW (1): 2-(4-(2,2,2-Trifluoroethoxy)phenyl)acetic acid (6.00 g, 25.6 mmol, reference: D. Page, et al. Bioorganic Med. Chem. Lett. (2008), 18, 3695) was deprotonated with NaHMDS (2.0 M in THF, 38.4 mL, 77 mmol) and reacted with 1-chloro-4-iodobutane (8.40 g, 38.4 mmol) using a procedure analogous to Step AC (1) to afford 6-chloro-2-(4-(2,2,2-trifluoroethoxy)phenyl)hexanoic acid (4.32 g, 13.3 mmo, 52% yield) as a clear viscous oil that eventually formed a waxy solid. LC-MS (M−H)− 323.1. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.24-7.27 (m, 2 H), 6.90 (d, J=8.5 Hz, 2 H), 4.32 (q, J=7.9 Hz, 2 H), 3.45-3.56 (m, 3 H), 2.00-2.12 (m, 1 H), 1.71-1.83 (m, 3 H), 1.29-1.49 (m, 2 H).
Sources & evidence
- ORD record
- ord-791dd016b6f741b38d6b1043fbb4f158
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349880B2
Reaction notes
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