Tert-butyl 4-(chloromethyl)benzoate

Oxalyl chloride (101 mL) was added dropwise over a 30 min period to a slurry of 4-chloromethyl benzoic acid (181.8 g) in dichloromethane (1.2L) containing 5 mL of DMF. After the addition was complete the reaction mixture was stirred at room temperature for 24h, concentrated under reduced pressure and then co-evaporated with toluene. To the residue was added 908 mL of MTBE and the mixture was cooled to -5 Step 1: 4-Chloromethyl benzoic aci Oxalyl chloride (101 mL) was added dropwise over a 30 min period to a slurry of 4- chloromethyl benzoic acid (181.8 g) in dichloromethane (1.2L) containing 5 mL of DMF. After the addition was complete the reaction mixture was stirred at room temperature for 24h, concentrated under reduced pressure and then co-evaporated with toluene. To the residue was added 908 mL of MTBE and the mixture was cooled to -5 °C. A solution of potassium tert- butoxide in THF (1.0 M, 1172 mL) was added dropwise ensuring that the internal temperature remained below 10 °C. After the addition was complete, the reaction mixture was stirred for an additional 1 hour then treated with 500 mL of saturated sodium bicarbonate solution. After stirring 5 minutes, then settling, the organic phase was separated, washed with saturated sodium chloride solution and dried over magnesium sulfate. Concentration yielded 241.7g (86percent yield) as a dark oil. HNMR: CDC1To a reactor were added 2-(4-bromophenyl)acetic acid (reagent 5, 36.0Kg, 1.0X, l.Oeq), DMF (237Kg, 6.5-7. OX), and THF (90Kg, 2.4-2.5X). The reactor was cooled to - l5-0C. To this mixture was added LiHMDS (335Kg, 9.1-9.3X, lmol/L) at -l5-0C. The mixture was stirred at -l5-0C for 2-3h. HPLC showed that the ratio of reagent 5/intermediate 7 is about 3.9%. The reaction was quenched by 1N HC1 (774Kg, 17-20X) at -l0-l0C and diluted by EtOAc (35lKg, 9X-10X). The mixture was stirred for 30-60 min. The organic layer was separated. The aqueous layer was extracted with EtOAc (35lKg, 9X-10X). The organic layers were combined and washed with process water (9.5-10.5X) 3 times (370Kg+370Kg+365Kg). Then the organic solution was concentrated to 5X-6X. EtOAc (440Kg, 12X-15X) was added to the reactor. The organic solution was concentrated to 5X-6X again for the next step without further purification (KF = 0.2%; residual THF = 1.0%; residual DMF = 0.1%, assay of intermediate 7 = 21.9%).454 mg (2 mmol) of

Molecular Weight:226.70
XLogP3:3.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:4
Exact Mass:226.0760574
Monoisotopic Mass:226.0760574
Topological Polar Surface Area:26.3
Heavy Atom Count:15
Complexity:212
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes