Benzyl chloroformate → HCID 86666947, compound

HRID 511026Notes

Reaction equation

HRID 511026 reaction equation
[NH2:1][CH:2]([C:4]1[C:5]([O:23][CH3:24])=[C:6]([CH:12]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:13]2)[C:7]([Cl:11])=[C:8]([Cl:10])[CH:9]=1)[CH3:3].CCN(C(C)C)C(C)C.Cl[C:35]([O:37][CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:36]>C(Cl)Cl>[CH2:38]([O:37][C:35]([NH:1][CH:2]([C:4]1[C:5]([O:23][CH3:24])=[C:6]([CH:12]2[CH2:15][N:14]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:13]2)[C:7]([Cl:11])=[C:8]([Cl:10])[CH:9]=1)[CH3:3])=[O:36])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 86666946HCID 86666946, compound

Product 1

HCID 86666947HCID 86666947, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of tert-butyl 3-[3-(1-aminoethyl)-5,6-dichloro-2-methoxyphenyl]azetidine-1-carboxylate (4.1 g, 9.7 mmol) and DIPEA (3.4 mL, 20 mmol) in methylene chloride (49 mL) at 0° C. was treated with benzyl chloroformate (1.8 mL, 13 mmol) and stirred at 20° C. for 1 hour. The reaction mixture was diluted with dichloromethane (300 mL), washed with saturated sodium bicarbonate solution, water, and brine, dried with sodium sulfate, filtered and concentrated to a crude residue that was purified by flash column chromatography using EtOAc in hexanes (5%-40%) to give the desired racemic product (4 g, 81%). This racemic material was separated by chiral HPLC (ChiralPak AD-H column, 20×250 mm, 5 micron particle size, eluting with 30% ethanol in hexanes at 12 mL/min, column loading ˜135 mg/injection) to give the desired peak 2 isomer (1.9 g, 38%). Peak 2 isomer: LCMS for C25H30Cl2N2O5Na (M+Na)+: m/z=531.2. Found: 531.2.

Workup

  1. washwashed with saturated sodium bicarbonate solution, water, and brine
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated to a crude residue that
  5. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-88004aa3f9954b3eb023551c0c79740a
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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