Isopropyl chloroformate → (3S,4S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic Acid Isopropyl Ester Hydrochloride

HRID 1182172Notes

Reaction equation

HRID 1182172 reaction equation
[CH3:1][O:2][C:3]1[CH:32]=[CH:31][C:6]([CH2:7][N:8]2[CH2:12][CH2:11][C:10]3([CH2:17][CH2:16][N:15]([CH2:18][C@@H:19]4[C@@H:23]([C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:22][NH:21][CH2:20]4)[CH2:14][CH2:13]3)[C:9]2=[O:30])=[CH:5][CH:4]=1.[CH:33]([O:36][C:37]([Cl:39])=[O:38])([CH3:35])[CH3:34].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[ClH:39].[CH:33]([O:36][C:37]([N:21]1[CH2:22][C@H:23]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[C@@H:19]([CH2:18][N:15]2[CH2:16][CH2:17][C:10]3([C:9](=[O:30])[N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:32][CH:31]=4)[CH2:12][CH2:11]3)[CH2:13][CH2:14]2)[CH2:20]1)=[O:38])([CH3:35])[CH3:34]

Participants

6

Reactant 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 114646642-(4-Methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one

Product 1

HCID 67368814(3S,4S)-3-[2-(4-Methoxy-benzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-ylmethyl]-4-phenyl-pyrrolidine-1-carboxylic Acid Isopropyl Ester HydrochlorideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(4-methoxy-benzyl)-8-((3R,4S)-4-phenyl-pyrrolidin-3-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one (60 μmol) in anhydrous DCM (1 mL) was added isopropylchloroformate (180 μL, 1M in toluene, 180 μmol) and triethylamine (29 μL, 55 μmol). The reaction mixture was stirred overnight at room temperature. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture and the aqueous layer washed with dichloromethane (3×2 mL). The organic layer was then concentrated in vacuo and purified by semi-preparative HPLC (Method D) and lyophilized to give the Compound 183 as a colorless solid (15.3 mg, 50%).

Workup

  1. washthe aqueous layer washed with dichloromethane (3×2 mL)
  2. concentrationThe organic layer was then concentrated in vacuo
  3. custompurified by semi-preparative HPLC (Method D)

Sources & evidence

ORD record
ord-b70cd91e2a464b3f99dfe0e0782d4201
Source dataset
uspto-grants-2007_10
Patent number
US07288548B2

Reaction notes

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