Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate → methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate

HRID 927973Notes

Reaction equation

HRID 927973 reaction equation
C[C:2]1[C:3]([CH:13]2[CH2:16][N:15]([C:17](=[O:22])[C:18]([F:21])([F:20])[F:19])[CH2:14]2)=[C:4]([S:9](Cl)(=[O:11])=[O:10])[CH:5]=[CH:6][C:7]=1[F:8].[NH2:23][C:24]1[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]2[C:27]([CH:28]3[CH2:38][CH:29]3[CH2:30][O:31]2)=[CH:26][CH:25]=1>N1C=CC=CC=1.C(Cl)Cl>[F:8][C:7]1[CH:6]=[CH:5][C:4]([S:9]([NH:23][C:24]2[C:33]([C:34]([O:36][CH3:37])=[O:35])=[C:32]3[C:27]([CH:28]4[CH2:38][CH:29]4[CH2:30][O:31]3)=[CH:26][CH:25]=2)(=[O:10])=[O:11])=[C:3]([CH:13]2[CH2:14][N:15]([C:17](=[O:22])[C:18]([F:20])([F:19])[F:21])[CH2:16]2)[CH:2]=1

Participants

5

Reactant 2

HCID 86713293Methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×HCID 86713313Methyl 4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzenesulfonyl chloride2×

Product 1

HCID 86713312methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzene-sulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylateYield 104.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A solution of methyl 4-fluoro-2-[1-(2,2,2-trifluoroacetyl)azetidin-3-yl]benzenesulfonyl chloride (Intermediate 89, 0.192 g) and methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (Intermediate 42, 0.122 g) in pyridine (1 mL) and DCM (3 mL) was left to stand at room temperature for 18 hours. The mixture was diluted with DCM, washed with 1M hydrochloric acid and filtered through a phase separator. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30% to give methyl (1aRS,7bSR)-5-{4-fluoro-2-[1-(2,2,2-trifluoro-acetyl)azetidin-3-yl]benzenesulfonylamino}-1,1a,2,7b-tetrahydrocyclopropa-[c]chromene-4-carboxylate (0.294 g) as a colourless gum.

Workup

  1. washwashed with 1M hydrochloric acid
  2. filtrationfiltered through a phase separator
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by chromatography on silica
  5. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 0-30%

Sources & evidence

ORD record
ord-baf4c76619c741e08abc8716f3035ef0
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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