Methyl chloroformate → methyl (S)-1-(4-bromophenyl)ethyl(4-(4-fluorophenyl)-4-oxobutan-2-yl)carbamate

HRID 2037463Notes

Reaction equation

HRID 2037463 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH:10][CH:11]([CH3:22])[CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:14])[CH3:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:29](Cl)(=[O:32])[O:30][CH3:31]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]([CH:11]([CH2:12][C:13]([C:15]2[CH:16]=[CH:17][C:18]([F:21])=[CH:19][CH:20]=2)=[O:14])[CH3:22])[C:29](=[O:32])[O:30][CH3:31])[CH3:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6586Methyl chloroformateHCID 11430Potassium CarbonateHCID 581091753-((S)-1-(4-bromophenyl)ethylamino)-1-(4-fluorophenyl)butan-1-one

Product 1

HCID 58109342methyl (S)-1-(4-bromophenyl)ethyl(4-(4-fluorophenyl)-4-oxobutan-2-yl)carbamateYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-((S)-1-(4-bromophenyl)ethylamino)-1-(4-fluorophenyl)butan-1-one (28.8 g, 79.2 mmol) and K2CO3 (100 g, 0.79 mol) in methylene chloride (1000 mL) was added methyl carbonochloridate (100 g, 0.72 mol) at 0° C. The formed mixture was stirred at rt overnight. The mixture was filtered and concentrated to give the crude product, which was purified by preparative HPLC to give methyl (S)-1-(4-bromophenyl)ethyl(4-(4-fluorophenyl)-4-oxobutan-2-yl)carbamate (7.5 g, 23%). 1H NMR (400 MHz, CDCl3): δ=1.28 (d, 3H), 1.52 (d, 3H), 2.59 (m, 1H), 3.72 (m, 5H), 5.43 (m, 1H), 6.98 (m, 3H), 7.16 (m, 2H), 7.31 (m, 2H), 7.60 (m, 2H).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customto give the crude product, which
  4. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-c069d82bcb234c0fac36421c80a646e5
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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