1-Chloro-4-iodobutane → 6-Chloro-2-(4-(difluoromethoxy)phenyl)hexanoic acid

HRID 1803206Notes

Reaction equation

HRID 1803206 reaction equation
[F:1][CH:2]([F:14])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]([OH:13])=[O:12])=[CH:6][CH:5]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Cl:25][CH2:26][CH2:27][CH2:28][CH2:29]I>CCOC(C)=O.CCCCCC>[Cl:25][CH2:26][CH2:27][CH2:28][CH2:29][CH:10]([C:7]1[CH:6]=[CH:5][C:4]([O:3][CH:2]([F:14])[F:1])=[CH:9][CH:8]=1)[C:11]([OH:13])=[O:12]

Participants

5

Reactant 3

HCID 825271-Chloro-4-iodobutaneHCID 2724254Sodium bis(trimethylsilyl)amideHCID 27741272-[4-(Difluoromethoxy)phenyl]acetic acid

Product 1

HCID 581100816-Chloro-2-(4-(difluoromethoxy)phenyl)hexanoic acidYield 15.61%

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Procedure

Step AZ (1): 2-(4-(Difluoromethoxy)phenyl)acetic acid (5.0 g, 24.8 mmol) was deprotonated with NaHMDS (2.0 M in THF, 24.7 mL, 49.5 mmol) and reacted with 1-chloro-4-iodobutane (3.03 g, 24.7 mmol) using a procedure analogous to Step AC (1) to afford after purification by silica gel column chromatography (0-70% EtOAc/hexane), 6-chloro-2-(4-(difluoromethoxy)phenyl)hexanoic acid (1.13 g, 3.86 mmol, 15.61% yield) as a pale-yellow oil. LC-MS (M−H)− 291.1. 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.30 (d, J=8.9 Hz, 2 H), 7.08 (d, J=8.5 Hz, 2 H), 6.29-6.66 (m, 1 H), 3.54 (t, J=7.6 Hz, 1 H), 3.49 (t, J=6.6 Hz, 2 H), 2.04-2.13 (m, 1 H), 1.72-1.82 (m, 3 H), 1.32-1.51 (m, 2 H).

Workup

  1. customto afford

Sources & evidence

ORD record
ord-df717cda1a9c4c08a0c7049f8af13c51
Source dataset
uspto-grants-2013_01
Patent number
US08349880B2

Reaction notes

Loading…