Acetyl chloride → HCID 89734152, compound

HRID 926401Notes

Reaction equation

HRID 926401 reaction equation
[C:1]1([C@H:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@@H:25]3[CH2:29][OH:30])=[O:23])[N:16]3[CH2:21][CH2:20][O:19][CH2:18][C:17]=23)=[O:12])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:38](Cl)(=[O:40])[CH3:39].C(=O)([O-])O.[Na+]>CN(C)C1C=CN=CC=1.ClCCl>[C:1]1([C@H:7]([NH:10][C:11]([C:13]2[CH:14]=[C:15]([C:22]([N:24]3[CH2:28][CH2:27][CH2:26][C@@H:25]3[CH2:29][O:30][C:38](=[O:40])[CH3:39])=[O:23])[N:16]3[CH2:21][CH2:20][O:19][CH2:18][C:17]=23)=[O:12])[CH2:8][CH3:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 89734073HCID 89734073, compound

Product 1

HCID 89734152HCID 89734152, compoundYield 55%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6-((R)-2-hydroxymethyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ((R)-1-phenyl-propyl)-amide (Comp. No. 16ei) (0.213 mmol), triethylamine (31 mg, 0.31 mmol), acetyl chloride (24 mg, 0.31 mmol) and 4-dimethylamino-pyridine (ca. 1 mg) in dry dichloromethane was stirred overnight. After addition of aqueous sodium hydrogencarbonate, extraction (3 times with dichloromethane), and drying of the combined organic layers over sodium sulfate, the solvents were evaporated and the residue was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid) to give acetic acid (R)-1-[8-((R)-1-phenyl-propylcarbamoyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-6-carbonyl]-pyrrolidin-2-ylmethyl ester (54 mg, 55%). LC/MS (method 4): Rt=1.23 min; m/z=454.31 (M+H+).

Workup

  1. dry with materialdrying of the combined organic layers over sodium sulfate
  2. customthe solvents were evaporated
  3. customthe residue was purified by reverse phase HPLC (acetonitrile/water gradient with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-71ccd758dd2448a198168df6320c517a
Source dataset
uspto-grants-2016_03
Patent number
US09284333B2

Reaction notes

Loading…