tert-butyl (S)-3-(2-chlorosulfonyl-5-fluorobenzyloxy)pyrrolidine-1-carboxylate → tert-butyl (S)-3-[(1aR,7bS)-5-fluoro-2-(4-methoxycarbonyl-1,1a,2,7b-tetrahydro-cyclopropa[c]chromen-5-ylsulfamoyl)benzyloxy]pyrrolidine-1-carboxylate

HRID 928069Notes

Reaction equation

HRID 928069 reaction equation
Cl[S:2]([C:5]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:6]=1[CH2:7][O:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1)(=[O:4])=[O:3].[NH2:26][C:27]1[C:36]([C:37]([O:39][CH3:40])=[O:38])=[C:35]2[C:30]([C@H:31]3[CH2:41][C@H:32]3[CH2:33][O:34]2)=[CH:29][CH:28]=1>C(Cl)Cl>[F:25][C:22]1[CH:23]=[CH:24][C:5]([S:2](=[O:4])(=[O:3])[NH:26][C:27]2[CH:28]=[CH:29][C:30]3[C@H:31]4[CH2:41][C@H:32]4[CH2:33][O:34][C:35]=3[C:36]=2[C:37]([O:39][CH3:40])=[O:38])=[C:6]([CH:21]=1)[CH2:7][O:8][C@H:9]1[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1

Participants

4

Reactant 2

HCID 86713368tert-butyl (S)-3-(2-chlorosulfonyl-5-fluorobenzyloxy)pyrrolidine-1-carboxylate2×HCID 86713369(1AR,7bS)-methyl 5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate2×

Product 1

HCID 71007006tert-butyl (S)-3-[(1aR,7bS)-5-fluoro-2-(4-methoxycarbonyl-1,1a,2,7b-tetrahydro-cyclopropa[c]chromen-5-ylsulfamoyl)benzyloxy]pyrrolidine-1-carboxylateYield 99.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of tert-butyl (S)-3-(2-chlorosulfonyl-5-fluorobenzyloxy)pyrrolidine-1-carboxylate (Intermediate 215, 0.295 g) in DCM (2 mL) was added to a solution of methyl (1aR,7bS)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 42A, 0.11 g) in DCM (2 mL) and the mixture was left at room temperature for 5 days. The mixture was diluted with DCM, washed with 1M hydrochloric acid and filtered through a phase separator. The filtrate was evaporated 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 tert-butyl (S)-3-[5-fluoro-2-((1aR,7bS)-4-methoxycarbonyl-1,1a,2,7b-tetrahydrocyclopropa-[c]chromen-5-ylsulfamoyl)benzyloxy]pyrrolidine-1-carboxylate (0.288 g) as a white foam.

Workup

  1. washwashed with 1M hydrochloric acid
  2. filtrationfiltered through a phase separator
  3. customThe filtrate was evaporated 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-aab89980612440f3b040931aae34ca04
Source dataset
uspto-grants-2016_03
Patent number
US09290472B2

Reaction notes

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