Tert-butoxycarbonylalanine → [(S)-1-(8-Fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-5-ylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 243222Notes

Reaction equation

HRID 243222 reaction equation
[F:1][C:2]1[C:11]2[O:10][CH2:9][CH2:8][NH:7][C:6]=2[C:5]([NH2:12])=[CH:4][CH:3]=1.[C:13]([O:17][C:18]([NH:20][C@@H:21]([CH3:25])[C:22](O)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:13]([O:17][C:18](=[O:19])[NH:20][C@H:21]([C:22](=[O:23])[NH:12][C:5]1[C:6]2[NH:7][CH2:8][CH2:9][O:10][C:11]=2[C:2]([F:1])=[CH:3][CH:4]=1)[CH3:25])([CH3:14])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 85082Tert-butoxycarbonylalanineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 681576428-Fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-5-ylamine

Product 1

HCID 68158273[(S)-1-(8-Fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-5-ylcarbamoyl)ethyl]carbamic acid tert-butyl esterYield 89.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To an ice-cooled mixture of 8-fluoro-3,4-dihydro-2H-benzo[1,4]oxazin-5-ylamine (243 mg, 1.445 mmol), (S)-2-tert-butoxycarbonylaminopropionic acid (305 mg, 1.61 mmol) and HOAt (200 mg, 1.463 mmol) in DCM (15 mL) was added EDCI HCl (337 mg, 1.76 mmol). The reaction mixture was stirred in the ice bath for 90 min, then diluted with DCM, washed with aqueous Na2CO3 and then water. The organic layer was dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 50-70% EtOAc in cyclohexane) affording the title compound as a pale yellow foam (440 mg, 89%). LCMS (Method B): RT 3.02 min [M+H]+ 340

Workup

  1. washwashed with aqueous Na2CO3
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 50-70% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-03ed6704ecff45fb911ec66b579c58f2
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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