1,1'-Carbonyldiimidazole → HCID 86762757, compound

HRID 876725Notes

Reaction equation

HRID 876725 reaction equation
[CH2:1]([N:4]1[CH2:8][C@@:7]([NH2:16])([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Br:15])[CH:10]=2)[C@H:6]([CH2:17]O)[CH2:5]1)[CH:2]=[CH2:3].[C:19]([N:27]=[C:28]=[S:29])(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>O1CCCC1>[CH2:1]([N:4]1[CH2:5][C@@H:6]2[C@@:7]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([Br:15])[CH:10]=3)([N:16]=[C:28]([NH:27][C:19](=[O:26])[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[S:29][CH2:17]2)[CH2:8]1)[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 68284Benzoyl isothiocyanateHCID 86762758[(3R,4S)-1-allyl-4-amino-4-(3-bromophenyl)pyrrolidin-3-yl]methanol

Product 1

HCID 86762757HCID 86762757, compoundYield 68.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
22 °C

Procedure

A solution of [(3R,4S)-1-allyl-4-amino-4-(3-bromophenyl)pyrrolidin-3-yl]methanol (27 g; 86.7 mmol) in tetrahydrofuran (270 mL) is cooled to −5° C. under a nitrogen atmosphere. Benzoyl isothiocyanate (12.3 mL, 91 mmol) is added drop wise keeping the temperature below 0° C. The reaction is allowed to warm to 22° C. over 1 hour. 1,1′-Carbonyldiimidazole (28.1 g, 173.5 mmol) is added in a single portion and the reaction is stirred for 1 hour at 22° C. and then heated to reflux for 16 hours. The solvent is removed in vacuo and the residue dried under vacuum. The crude material is partitioned in methyl tert-butyl ether (500 mL) and water (250 mL). The organic layer is separated, dried over magnesium sulfate, filtered and evaporated to dryness. The crude material is purified over a silica gel gradient of 90/10 to 60/40 methylene chloride/ethyl acetate to give the title compound (27 g, 68%). ES/MS (m/e): 456 (M+1).

Workup

  1. customthe temperature below 0° C
  2. temperatureheated
  3. temperatureto reflux for 16 hours
  4. customThe solvent is removed in vacuo
  5. customthe residue dried under vacuum
  6. customThe crude material is partitioned in methyl tert-butyl ether (500 mL)
  7. customThe organic layer is separated
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customThe crude material is purified over a silica gel gradient of 90/10 to 60/40 methylene chloride/ethyl acetate

Sources & evidence

ORD record
ord-e5ff4a2e3064472394dfec7e3243e5a9
Source dataset
uspto-grants-2015_03
Patent number
US08987254B2

Reaction notes

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