1-Chloro-4-iodobutane → 6-Chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid
Reaction equation
[F:1][CH:2]([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:26][CH2:27][CH2:28][CH2:29][CH2:30]I>>[Cl:26][CH2:27][CH2:28][CH2:29][CH2:30][CH:11]([C:8]1[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH:2]([F:15])[F:1])=[CH:10][CH:9]=1)[C:12]([OH:14])=[O:13]Participants
4
Procedure
Step AX (2): 2-(4-(2,2-Difluoroethoxy)phenyl)acetic acid (6.00 g, 27.8 mmol) was deprotonated with NaHMDS (2.0 M in THF, 41.6 mL, 83 mmol) and reacted with 1-chloro-4-iodobutane (9.10 g, 41.6 mmol) using a procedure analogous to Step AC (1) to afford 6-chloro-2-(4-(2,2-difluoroethoxy)phenyl)hexanoic acid (6.94 g, 21.5 mmol, 77% yield) as a viscous oil that slowly solidified at rt to afford an off-white solid. LC-MS (M−H)− 305.21. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.24 (d, J=8.9 Hz, 2 H), 6.87 (d, J=8.5 Hz, 2 H), 5.88-6.23 (m, 1 H), 4.15 (td, J=13.0, 4.1 Hz, 2 H), 3.44-3.53 (m, 3 H), 1.99-2.12 (m, 1 H), 1.70-1.86 (m, 3 H), 1.31-1.50 (m, 2 H).
Sources & evidence
- ORD record
- ord-0b2f45e5b8254823953dcf38585192b5
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349880B2
Reaction notes
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