Diisopropylethylamine → rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-cyclopropyl-carbamic acid 4-fluoro-phenyl ester

HRID 527488Notes

Reaction equation

HRID 527488 reaction equation
[CH2:1]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=2)[C@H:10]([NH:20][CH:21]2[CH2:23][CH2:22]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:34]([O:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][CH:38]=1)=[O:35]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:43][C:40]1[CH:41]=[CH:42][C:37]([O:36][C:34](=[O:35])[N:20]([C@H:10]2[C@H:11]([C:13]3[CH:14]=[CH:15][C:16]([Cl:19])=[CH:17][CH:18]=3)[CH2:12][N:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH2:9]2)[CH:21]2[CH2:22][CH2:23]2)=[CH:38][CH:39]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 27332564-Fluorophenyl chloroformateHCID 58312614rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-cyclopropyl-amine

Product 1

HCID 58312679rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-cyclopropyl-carbamic acid 4-fluoro-phenyl esterYield 51%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 2.27 g (6.94 mmol) rac-[(3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-cyclopropyl-amine, 987 mg (7.64 mmol) DIPEA, 8.48 mg (0.07 mmol) DMAP and 1.27 g (7.29 mmol) 4-fluorophenyl chloroformate in 40 mL DCM at 0° C. was stirred at room temperature over night and evaporated to dryness. the residue was purified by column chromatography on silica eluting with a gradient formed from TBME and heptane. The product containing fractions were evaporated to yield 1.64 g (51%) of the title compound as colorless viscous oil. MS m/e: 465.1 [M+H]+.

Workup

  1. customevaporated to dryness
  2. customthe residue was purified by column chromatography on silica eluting with a gradient
  3. customformed from TBME and heptane
  4. additionThe product containing fractions
  5. customwere evaporated

Sources & evidence

ORD record
ord-3e291aa19329438fa33dfc69183c50a6
Source dataset
uspto-grants-2016_05
Patent number
US09346786B2

Reaction notes

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