Reaction SMILES: [CH2:1]([OH:21])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH3:20].Br[CH:23]([CH2:27][CH3:28])[C:24]([OH:26])=[O:25].CC([O-])(C)C.[Na+].C(O)=O.Cl>CC(OC)(C)C.O.C1(C)C=CC=CC=1.C1COCC1>[CH2:1]([O:21][CH:23]([CH2:27][CH3:28])[C:24]([OH:26])=[O:25])[CH2:2][CH2:3][CH2:4]/[CH:5]=[CH:6]\[CH2:7]/[CH:8]=[CH:9]\[CH2:10]/[CH:11]=[CH:12]\[CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH3:20]
Reactant: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCCO
Reactant: CCC(Br)C(=O)O
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: O
Solvent: Cc1ccccc1
Product: CC/C=C\C/C=C\C/C=C\C/C=C\C/C=C\CCCCOC(CC)C(=O)O
Temperature: 7.5 °C
Reaction time: 0.75 h

Procedure:
(5Z,8Z,11Z,14Z,17Z)-Icosa-5,8,11,14,17-pentaen-1-ol (2) (25 kg, 1.0 eq.), THF (235 kg), toluene (7 kg) and 2-bromobutyric acid (21.5 kg. 1.5 eq.) were charged into a reactor at ambient temperature. The BHT level was adjusted to 3000 ppm. The reaction mixture was cooled to 5-10° C. Over a period of 30-60 minutes, 117.6 kg of a 17% solution of NaOtBu (20 kg active content, 2.4 eq.) in MTBE was added. After the addition was complete, the reaction was stirred for 30 minutes at 5-10° C. Over a period of 30 minutes, 19.4 kg of a 17% solution of NaOtBu (0.4 eq.) in MTBE was added. After the addition was complete, the reaction was stirred for 60 minutes at 5-10° C. Over a period of 30 minutes, 2-bromobutyric acid (14.5 kg, 1.0 eq.) was added. After the addition was complete, the reaction was stirred for 60 minutes at 5-10° C. Over a period of 30 minutes, 40 kg of a 17% solution of NaOtBu (0.8 eq.) in MTBE was added. After the addition was complete, the reaction was stirred for 60 minutes at 5-10° C. Over a period of 30 minutes, 19.4 kg of a 17% solution of NaOtBu (0.4 eq.) in MTBE was added. After the addition was complete, the reaction was stirred for 60 minutes at 5-10° C. The reaction temperature was maintained between 5-10° C., and formic acid (2 kg, 0.5 eq.) and water (66 kg) were added. The reaction was stirred at 15-25° C., and the pH was adjusted to 2-2.5 using 1:1 concentrated HCl and DI water. The organic and aqueous phases were separated, and the aqueous phase was extracted with MTBE (2×44 kg). The combined organic phases were washed three times with DI water (66 kg). If necessary the organic phase can be washed a fourth time with DI water. The organic phase was dried over Na2SO4 (20.0 kg) and Celite (5.0 kg) and the solids were filtered and washed with MTBE (15 kg). The organic phase was evaporated using a thin film evaporator. The crude product mixture (Crude A) was dissolved in 2-methyltetrahydrofuran (2-MeTHF) (140 kg), and washed three times with a saturated aqueous NaHCO3 solution (70 kg) and then with a saturated aq. NaCl solution (70 kg). Optionally, the washing procedure is repeated to remove remaining 2-bromobutyric acid and/or crotonic acid. 2-MeTHF (710 kg) and DI water (710 kg) were added to the crude product (Crude B), and the pH was adjusted to 12-13 with a 50% aq. NaOH solution to transfer the product to the aqueous phase. The mixture was stirred for 30 minutes, and then the phases were allowed to separate. The phases were separated and 2-MeTHF (700 kg) was added to the aqueous phase and the mixture was stirred for 30 minutes. The phases were again allowed to separate and the phases were separated. The aqueous phase was clarified with charcoal (2.5 kg) and Celite (5.5 kg), and the solids were filtered and washed with 30 kg of 20% aqueous NaOH. The combined aqueous phase was clarified with Celite (5.5 kg), and the solids were filtered and washed with 30 kg of 20% aqueous NaOH. The pH was adjusted to 2-2.5 with conc. HCl(aq.), and the resulting mixture was extracted with MTBE (3×55 kg). The combined organic phases were washed with DI water (74 kg). The organic phase was concentrated by passing through a thin film evaporator twice. The residue was dissolved in pentane (135 kg), and clarified using silica (2 kg) twice, filtering each time and washing with pentane (17.5 kg). BHA stabilizer (0.03%) was added. The mixture was filtered on 0.5 □m filter, and the solvent was evaporated in vacuo to obtain 2-((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenyloxy)butanoic acid (3). The total yield starting from EPA ethyl ester (1) was about 65%. The purity was determined to be 96% by HPLC.