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.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=CO
Solvent: C1CCOC1
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,11Z14Z,17Z)-Icosa-5,8,11,14,17-pentaen-1-ol (2) (10 kg, 1.0 eq.), THF (94 kg), and 2-bromobutyric acid (8.6 kg, 1.5 eq.) were charged into a reactor at ambient temperature. The reaction mixture was cooled to 5-10° C. Over a period of 30-60 minutes, 47 kg of a 17% solution of NaOtBu (8 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. Over a period of 30 minutes, 7.6 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 (5.8 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, 15.9 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, 7.7 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 (0.8 kg, 0.5 eq.) and water (26.5 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 (2×17.6 kg). The combined organic phases were washed three times with DI water (26.6 kg). If necessary the organic phase can be washed a fourth time with DI water. The organic phase was clarified with Celite (2.0 kg) and Na2SO4 (8.0 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 was dissolved in 2-methyltetrahydrofuran (2-MeTHF) (48 kg), and washed three times with a saturated aqueous NaHCO3 solution (28 kg) and then with a saturated aq. NaCl solution (27.5 kg). Optionally, the washing procedure is repeated to remove remaining 2-bromobutyric acid and/or crotonic acid. 2-MeTHF (282 kg) and DI water (285 kg) were added to the crude product, 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 for at least 30 minutes. The phases were separated and 2-MeTHF (280 kg) was added to the aqueous phase and the mixture was stirred for 30 minutes. The phases were again allowed to separate for at least 30 minutes and the phases were separated. The aqueous phase was clarified with Celite (2.2 kg) and charcoal (1 kg), and the solids were filtered and washed with 12 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 (3×22 kg). The combined organic phases were washed with DI water (30 kg), and the organic phase was clarified with silica (9.4 kg), and the solids were filtered and washed with MTBE (20 kg). The organic phase was concentrated by passing through a thin film evaporator twice. The residue was dissolved in pentane (54 kg), and clarified using silica (0.8 kg) twice, filtering each time and washing with pentane (7 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 53%. The purity was determined to be 96.9% by HPLC.