4-Methylmorpholine → [(1S,2R)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester

HRID 242920Notes

Reaction equation

HRID 242920 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[CH2:16]([O:23][C@H:24]([CH3:37])[C@H:25]([NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:26](O)=[O:27])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1C=NC2N(O)N=NC=2C=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:33]([O:32][C:30](=[O:31])[NH:29][C@H:25]([C:26](=[O:27])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C@H:24]([O:23][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH3:37])([CH3:35])([CH3:34])[CH3:36]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 1549483L-Threonine, N-[(1,1-dimethylethoxy)carbonyl]-O-(phenylmethyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 214506204-Fluoro-2-phenylaminoaniline

Product 1

HCID 68158123[(1S,2R)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl esterYield 102.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (525 mg, 2.6 mmol), (2S,3R)-3-benzyloxy-2-tertbutoxycarbonylaminobutyric acid (880 mg, 2.9 mmol), HOAt (390 mg, 2.9 mmol), 4-methylmorpholine (0.60 mL, 5.7 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (560 mg, 2.9 mmol) in DCM (13 mL) was stirred at RT for 18 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic phase was washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(1S,2R)-2-benzyloxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)propyl]carbamic acid tert-butyl ester (1.32 g). LCMS (Method B): RT 4.32 min [M+H]+ 494.3.

Workup

  1. customThe reaction mixture was partitioned between DCM
  2. washThe organic phase was washed with brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

Sources & evidence

ORD record
ord-59ad941441e14ee786917867c0da5373
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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