Hydrochloric Acid → 1,1-Dimethylethyl N-[(1S)-1-(3-fluorophenyl)-3-oxopropyl]carbamate

HRID 1635969Notes

Reaction equation

HRID 1635969 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1)[CH2:10][C:11](OC)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].C([Al+]CC(C)C)C(C)C.CO.Cl>C(Cl)Cl.C1(C)C=CC=CC=1>[O:12]=[CH:11][CH2:10][C@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:2])[CH3:4])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 21225700DiisobutylaluminumhydrideHCID 57318280Methyl (βS)-β-[[(1,1-dimethylethoxy)carbonyl]amino]-3-fluorobenzenepropanoate

Product 1

HCID 590339311,1-Dimethylethyl N-[(1S)-1-(3-fluorophenyl)-3-oxopropyl]carbamate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirring solution of the methyl ester from Example 11, Step A (2.0 mmol, 594 mg) in 20 mL of dry DCM cooled to −78° C under nitrogen was added dropwise over 20 min. Diisobutylaluminum hydride (4 mmol, 4 mL of a 4 M solution in toluene). The reaction was stirred for 2 h at −78° C. after which time MeOH (4 mL) cooled to −78° C. was canulated into the reaction mixture. After 10 min. the solution was allowed to reach room temperature. DCM (30 mL) was added to the reaction, and the solution was poured into 60 mL of 2N HCl. The organic phase was collected and the aqueous phase was extracted with DCM (2×20 mL). The combined organic phase was dried with MgSO4 and concentrated under reduced pressure. The aldehyde was further purified by flash chromatography on silica gel (40 g) using a step gradient of 0% to 16% EtOAc/hexanes, increasing in 4% increments. The aldehyde eluted in 12-16% EtOAc/hexanes, affording a white waxy solid. 1H NMR (500 MHz, CDCl3): δ 9.76 (s, 1H), 7.28-7.4 (m, 1H); 7.11 (d, 1H, J=7.7 Hz); 7.04 (dd, 1H, J=9.8 Hz, 2.0 Hz), 6.96-7.02 (m, 1H), 5.25 (br s, 1H), 2.92-3.1 (2H, m), 1.45 (s, 9H). MS (ESI): m/z 250 (M+H).

Workup

  1. additionwas added dropwise over 20 min
  2. customto reach room temperature
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was extracted with DCM (2×20 mL)
  5. dry with materialThe combined organic phase was dried with MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe aldehyde was further purified by flash chromatography on silica gel (40 g)
  8. temperatureincreasing in 4% increments
  9. washThe aldehyde eluted in 12-16% EtOAc/hexanes
  10. customaffording a white waxy solid

Sources & evidence

ORD record
ord-4520cde31a494e658b9c01c84a93eed3
Source dataset
uspto-grants-2003_01
Patent number
US06511994B2

Reaction notes

Loading…