Methanesulfonic acid, 1,1,1-trifluoro-, calcium salt (2:1) → trans-3-[4-(4-Chloro-phenyl)-[1,4]diazepan-1-yl]4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1920103Notes

Reaction equation

HRID 1920103 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:14][CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH:26]2[CH:24]([O:25]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].FC(F)(F)S([O-])(=O)=O.[Ca+2].FC(F)(F)S([O-])(=O)=O>C(#N)C>[C:15]([O:19][C:20]([N:22]1[CH2:23][C@@H:24]([OH:25])[C@H:26]([N:11]2[CH2:12][CH2:13][CH2:14][N:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[CH2:9][CH2:10]2)[CH2:27]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

5

Reactant 3

HCID 2734307Methanesulfonic acid, 1,1,1-trifluoro-, calcium salt (2:1)HCID 10103880tert-Butyl 6-Oxa-3-azabicyclo(3.1.0)hexane-3-carboxylateHCID 213638201-(4-Chlorophenyl)-1,4-diazepane

Product 1

HCID 57982392trans-3-[4-(4-Chloro-phenyl)-[1,4]diazepan-1-yl]4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl esterYield 43.1%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(4-Chloro-phenyl)-[1,4]diazepane (1.00 g, 4.80 mmol) in acetonitrile (10 mL) was added 6-oxa-3-aza-bicyclo[3.1.0]hexane-3-carboxylic acid tert-butyl ester (0.925 g, 5.00 mmol) and calcium(II) trifluoromethanesulfonate (0.676 g, 2.00 mmol). The solution was stirred at 80° C. for 17 hours under nitrogen atmosphere. The reaction was concentrated in vacuo. The residue was diluted with saturated aqueous sodium bicarbonate (50 mL) and extracted with ethyl acetate (3×30 mL). The combined organics were washed with brine, dried over MgSO4, and evaporated. The residue was purified by silica gel chromatography (gradient ethyl acetate to 87:10:3 ethyl acetate:methanol:triethylamine) to yield 0.819 g (41%) of the title compound. ESI-MS m/z: 396 (M+1), FAS method rt: 1.25 min

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. additionThe residue was diluted with saturated aqueous sodium bicarbonate (50 mL)
  3. extractionextracted with ethyl acetate (3×30 mL)
  4. washThe combined organics were washed with brine
  5. dry with materialdried over MgSO4
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography (gradient ethyl acetate to 87:10:3 ethyl acetate:methanol:triethylamine)

Sources & evidence

ORD record
ord-2cf7f3f5aafd49a9af0243c25d811e4b
Source dataset
uspto-grants-2012_05
Patent number
US08168788B2

Reaction notes

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