Benzyl chloroformate → HCID 58303515, compound

HRID 1896216Notes

Reaction equation

HRID 1896216 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][C@@H:8]1[C@H:12]([CH2:13][F:14])[CH2:11][N:10](CC2C=CC=CC=2)[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.Cl[C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34]>CO.[Pd]>[CH2:36]([O:35][C:33]([N:10]1[CH2:11][C@@H:12]([CH2:13][F:14])[C@@H:8]([NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:22])[CH2:9]1)=[O:34])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1

Participants

6

Reactant 3

HCID 10387Benzyl chloroformateHCID 81531DiisopropylethylamineHCID 583035041,1-Dimethylethyl N-[(3R,4R)-4-(fluoromethyl)-1-(phenylmethyl)-3-pyrrolidinyl]carbamate

Product 1

HCID 58303515HCID 58303515, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of ((3R,4R)-1-Benzyl-4-fluoromethyl-pyrrolidin-3-yl)-carbamic acid tert-butyl ester (1 g, 3.24 mmol) in methanol (20 mL) was hydrogenated at 1 atm with 10% palladium on carbon (100 mg) for 24 hours. He crude reaction mixture was filter through celite then concentrate to an oil. The crude amine was dissolved in dichloromethane (8 ml) then cooled to 0 C and diisopropylethylamine (619 ul, 3.57 mmol) was added followed by benzyl chloroformate (507 ul, 3.57 mmol, 1.1 equiv.). The crude reaction was concentrated to an oil then purified by silica gel chromatography eluting with 0-20% EtOAc in Heptane which gave the title compound IXa of as a colorless oil (811 mg). 1H NMR (400 MHz, CHLOROFORM-d) 1.45 (s, 9H) 2.67 (br. s., 1H) 3.24-3.49 (m, 2H) 3.63-3.80 (m, 2H) 4.27-4.53 (m, 2H) 4.53-4.66 (m, 1H) 4.70 (dd, J=9.73, 4.93 Hz, 1H) 5.14 (br. s., 2H) 7.37 (br. s., 5H); LCMS: M+1−Boc=253.

Workup

  1. customHe crude reaction mixture
  2. filtrationwas filter through celite
  3. concentrationthen concentrate to an oil
  4. dissolutionThe crude amine was dissolved in dichloromethane (8 ml)
  5. additionwas added
  6. customThe crude reaction
  7. concentrationwas concentrated to an oil
  8. customthen purified by silica gel chromatography
  9. washeluting with 0-20% EtOAc in Heptane which

Sources & evidence

ORD record
ord-4065c076ae5f486fad2e41301ed633dd
Source dataset
uspto-grants-2013_08
Patent number
US08518952B2

Reaction notes

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