Sodium Sulfate → Phenylmethyl ({(3S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-3-pyrrolidinyl}methyl)carbamate

HRID 657058Notes

Reaction equation

HRID 657058 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH:13]=O)=[CH:4][CH:3]=1.[NH:16]1[CH2:20][CH2:19][C@@H:18]([CH2:21][NH:22][C:23](=[O:32])[O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:17]1.NC[C@H]1CCN(C(OC(C)(C)C)=O)C1.[O-]S([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.C(Cl)Cl>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][C:8](=[O:15])[N:9]2[CH2:12][CH2:13][N:16]2[CH2:20][CH2:19][C@@H:18]([CH2:21][NH:22][C:23](=[O:32])[O:24][CH2:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:17]2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 24436Sodium SulfateHCID 1515152tert-Butyl (3R)-3-(aminomethyl)pyrrolidine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 45072660benzyl ((R)-pyrrolidin-3-yl)methylcarbamateHCID 86635311(7-Fluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde

Product 1

HCID 86635345Phenylmethyl ({(3S)-1-[2-(7-fluoro-2-oxo-1(2H)-quinolinyl)ethyl]-3-pyrrolidinyl}methyl)carbamate

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (7-fluoro-2-oxo-1(2H)-quinolinyl)acetaldehyde (1.17 g, 5.71 mmol) and phenylmethyl [(3R)-3-pyrrolidinylmethyl]carbamate (may be prepared analogously to the 3R isomer of Preparation 23(b) in WO2006002047, from (R)-3-(aminomethyl)-1-N-Boc-pyrrolidine) (1.34 g, 5.71 mmol) in 1:1 CH2Cl2:MeOH (80 mL) were added 8 eq. Na2SO4 (6.5 g, 46 mmol) and the reaction was stirred at ambient temperature for 18 h. The intermediate imine was treated with sodium triacetoxyborohydride (3.63 g, 17.0 mmol) and stirred for an additional 16 h. The solvents were removed under reduced pressure; the residue was partitioned between ethyl acetate and aqueous saturated NaHCO3, and the organic layer was dried over Na2SO4. Purification by column chromatography on silica gel, (1% to 20% methanol:dichloromethane gradient) yielded a light amber oil. (820 mg, 34%).

Workup

  1. customThe solvents were removed under reduced pressure
  2. customthe residue was partitioned between ethyl acetate and aqueous saturated NaHCO3
  3. dry with materialthe organic layer was dried over Na2SO4
  4. customPurification by column chromatography on silica gel, (1% to 20% methanol:dichloromethane gradient)
  5. customyielded a light amber oil

Sources & evidence

ORD record
ord-9f35f219001b4e57aaf4d9cccf6c5107
Source dataset
uspto-grants-2011_12
Patent number
US08071592B2

Reaction notes

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