2-Dimethylaminopyridine → (3-Piperidin-4-yl-benzyl) carbamate

HRID 489622Notes

Reaction equation

HRID 489622 reaction equation
C(=O)([O-])O[C:3]1[CH:8]=[CH:7][C:6]([N+]([O-])=O)=[CH:5][CH:4]=1.Cl.C[Si](C)(C)C[CH2:18][O:19][C:20]([N:22]1CCC(C2C=CC=C(CN)C=2)CC1)=[O:21].CN([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][N:42]=1)C.C(N(C(C)C)CC)(C)C>CN(C)C=O>[C:20](=[O:21])([O:19][CH2:18][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([CH:45]2[CH2:46][CH2:41][NH:42][CH2:43][CH2:44]2)[CH:8]=1)[NH2:22]

Participants

6

Reactant 4

HCID 218852-DimethylaminopyridineHCID 81531DiisopropylethylamineHCID 21864993p-Nitrophenyl carbonateHCID 690309902-(Trimethylsilyl)ethyl 4-(3-(aminomethyl)phenyl)-piperidine-1-carboxylate hydrochloride

Product 1

HCID 67115226(3-Piperidin-4-yl-benzyl) carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

p-Nitrophenyl carbonate Wang resin (11.00 g, 15 mmol) and anhydrous dimethylformamide (100 ml) were placed in a peptide synthesis vessel and the resin was allowed to swell for 15 minutes. This was then treated with 4-(3-aminomethyl-phenyl)-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester hydrochloride (7.50 g, 21 mmol) in 50 ml dimethylformamide, dimethylaminopyridine (0.72, 6 mmol) and diisopropylethyl-amine. The peptide vessel was shaken at room temperature for 24 hours, then washed thoroughly with dimethylformamide (×5), methanol (×2), dimethylformamide (×2), methanol (×2), dichloromethane (×3), methanol (×2), dichloromethane (×2), methanol (×3), and dried. The resin was then treated with tetrahydrofuran to swell the resin and then allowed to drain. Then anhydrous tetrahydrofuran (100 ml) and tetrabutylammonium fluoride (75 ml, 1M in tetrahydrofuran) were added and the resin shaken for 18 hours. The resin was drained and washed with tetrahydrofuran (×5), methanol (×3), dichloromethane (×3), methanol (×3), dichloromethane (×3), methanol (×3) and dried to give (3-piperidin-4-yl-benzyl) carbamate Wang resin (12.30 g).

Workup

  1. washwashed thoroughly with dimethylformamide (×5), methanol (×2), dimethylformamide (×2), methanol (×2), dichloromethane (×3), methanol (×2), dichloromethane (×2), methanol (×3)
  2. customdried
  3. additionThe resin was then treated with tetrahydrofuran
  4. additionThen anhydrous tetrahydrofuran (100 ml) and tetrabutylammonium fluoride (75 ml, 1M in tetrahydrofuran) were added
  5. washwashed with tetrahydrofuran (×5), methanol (×3), dichloromethane (×3), methanol (×3), dichloromethane (×3), methanol (×3)
  6. customdried

Sources & evidence

ORD record
ord-9b0474b1e42c42e5b90a3e7dbb1afaa6
Source dataset
uspto-grants-2005_12
Patent number
US06977263B2

Reaction notes

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