4-Methylmorpholine → (S)-2-(4'-Ethoxycarbonyl-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl)-azetidine-1-carboxylic acid tert-butyl ester

HRID 1678502Notes

Reaction equation

HRID 1678502 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][C:18]([F:21])([F:20])[F:19])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)[CH:7]=1.[C:22]([O:26][C:27]([N:29]1[CH2:32][CH2:31][C@H:30]1[C:33]([OH:35])=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].CN(C(ON1N=N[C:46]2C=CC=C[C:45]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:32][CH2:31][C@H:30]1[C:33](=[O:35])[NH:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[CH:10][C:11]([C:14]([O:16][CH2:45][CH3:46])=[O:15])=[CH:12][CH:13]=2)[C:5]([O:17][C:18]([F:19])([F:20])[F:21])=[CH:4][CH:3]=1)=[O:28])([CH3:23])([CH3:24])[CH3:25]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2734495(2S)-1-((tert-butoxy)carbonyl)azetidine-2-carboxylic acidHCID 673729305'-Amino-2'-trifluoromethoxy-biphenyl-4-carboxylic acid

Product 1

HCID 67371803(S)-2-(4'-Ethoxycarbonyl-6-trifluoromethoxy-biphenyl-3-ylcarbamoyl)-azetidine-1-carboxylic acid tert-butyl esterYield 78.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 5′-amino-2′-trifluoromethoxy-biphenyl-4-carboxylic acid (150 mg), (S)-azetidine-1,2-dicarboxylic acid 1-tert-butyl ester (93 mg), HBTU (262 mg) and N-methyl morpholine (0.14 ml) in dry DMF (3 ml) was stirred at room temp for 18 h. The mixture was then partitioned between water and DCM. The dried organic layer was evaporated and the residue purified on silica gel. Elution with ethyl acetate:petrol 1:1 gave a pale orange oil (185 mg).

Workup

  1. customThe mixture was then partitioned between water and DCM
  2. customThe dried organic layer was evaporated
  3. customthe residue purified on silica gel
  4. washElution with ethyl acetate:petrol 1:1

Sources & evidence

ORD record
ord-65f520f383b24dc4a74c1939a07159ab
Source dataset
uspto-grants-2011_08
Patent number
US08008303B2

Reaction notes

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