Diisopropylethylamine → Tert-butyl (4-{4-[5-(4-fluorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]phenyl}cyclohexyl)acetate

HRID 1035692Notes

Reaction equation

HRID 1035692 reaction equation
[C:1]([O:5][C:6]([CH2:8][CH:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:24][C:25]1[CH:37]=[CH:36][C:28]([CH2:29][C:30]2[S:34][C:33]([NH2:35])=[N:32][N:31]=2)=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C)C=O.C(OCC)(=O)C>[F:24][C:25]1[CH:37]=[CH:36][C:28]([CH2:29][C:30]2[S:34][C:33]([NH:35][C:19]([C:18]3[CH:17]=[CH:16][C:15]([CH:12]4[CH2:13][CH2:14][CH:9]([CH2:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:10][CH2:11]4)=[CH:23][CH:22]=3)=[O:21])=[N:32][N:31]=2)=[CH:27][CH:26]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 7410595-[(4-Fluorophenyl)methyl]-1,3,4-thiadiazol-2-amineHCID 666854144-(4-Tert-butoxycarbonylmethylcyclohexyl)benzoic acid

Product 1

HCID 86662111Tert-butyl (4-{4-[5-(4-fluorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]phenyl}cyclohexyl)acetateYield 73.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

0.3 g of 4-(4-tert-butoxycarbonylmethylcyclohexyl)benzoic acid (0.94 mmol, 1 eq.) is placed in a mixture of 5 mL of dichloromethane and 2 mL of dimethylformamide at room temperature. 0.394 g of 5-(4-fluorobenzyl)-1,3,4-thiadiazol-2-amine (1.88 mmol, 2 eq.), 1.054 g of bromotris-pyrrolidinophosphonium hexafluorophosphonate (2.26 mmol, 2.4 eq.) and 0.66 mL of diisopropylethylamine (3.76 mmol, 4 eq.) are successively added. The reaction mixture is stirred for 6 days at room temperature, diluted in ethyl acetate, washed with saturated aqueous ammonium chloride solution, and washed twice with water and once with brine. The organic phase is concentrated and the residue is chromatographed on silica gel, eluting with a gradient of ethyl acetate in heptane ranging from 10% to 33%. 0.35 g of tert-butyl (4-{4-[5-(4-fluorobenzyl)[1.3.4]thiadiazol-2-ylcarbamoyl]phenyl}cyclohexyl)acetate is obtained.

Workup

  1. washwashed with saturated aqueous ammonium chloride solution
  2. washwashed twice with water and once with brine
  3. concentrationThe organic phase is concentrated
  4. customthe residue is chromatographed on silica gel
  5. washeluting with a gradient of ethyl acetate in heptane ranging from 10% to 33%

Sources & evidence

ORD record
ord-c16ae5f34701431eae9d020ed70b7030
Source dataset
uspto-grants-2013_10
Patent number
US08546391B2

Reaction notes

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