Isopropyl chloroformate → 1-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

HRID 2201326Notes

Reaction equation

HRID 2201326 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C@@H:9]([CH3:14])[CH2:10][C:11]([NH2:13])=[O:12])=[CH:4][CH:3]=1.Cl[C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17].CC(C)([O-])C.[Li+]>C(OCC)(=O)C.O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C@@H:9]([CH3:14])[CH2:10][C:11]([NH:13][C:16](=[O:17])[O:18][CH:19]([CH3:21])[CH3:20])=[O:12])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 7917Isopropyl chloroformateHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)HCID 67173762(S)-3-((4-Bromophenyl)amino)butanamide

Product 1

HCID 681848681-Methylethyl{(3S)-3-[(4-bromophenyl)amino]butanoyl}carbamate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3S)-3-[(4-bromophenyl)amino]butanamide (for a preparation see Intermediate 13, 24.9 g, 97 mmol) was taken up in Ethyl acetate (850 mL) and cooled to <−9° C. (internal). Isopropyl chloroformate (116 mL, 116 mmol, Aldrich) was added followed by slow addition of Lithium tert-butoxide (18.61 g, 232 mmol) in Tetrahydrofuran (THF) (232 mL) keeping the temperature below 0° C. The reaction was stirred for 30 mins then checked by LCMS which showed a complete reaction. The mixture was partitioned between EtOAc (1000 ml) and 2N HCl (2000 ml). The organic layer was washed with brine (2000 ml) and then dried with Na2SO4, filtered and concentrated to yield the product as a brown oil (17.9 g) LCMS (Method B): Rt=1.09, MH+=343

Workup

  1. temperaturecooled to <−9° C. (internal)
  2. customthe temperature below 0° C
  3. customa complete reaction
  4. customThe mixture was partitioned between EtOAc (1000 ml) and 2N HCl (2000 ml)
  5. washThe organic layer was washed with brine (2000 ml)
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b79b48adee6e41a2a5d650f8ef1d4adb
Source dataset
uspto-grants-2016_06
Patent number
US09360482B2

Reaction notes

Loading…