Diisopropylethylamine → 2-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexanecarboxamido)-3-cyclohexylpropylmethylcarbamate

HRID 2355359

Reaction equation

HRID 2355359 reaction equation
[C:1]([C@@H:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([C:15]([OH:17])=O)[CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:18][C@@H:19]([CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[CH2:20][NH:21][C:22](=[O:30])[O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27].[CH:38](N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>C(Cl)Cl.CCOCC.CN(C=O)C>[C:1]([CH:9]1[CH2:14][CH2:13][CH2:12][CH:11]([C:15]([NH:18][C@@H:19]([CH2:31][CH:32]2[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37]2)[CH2:20][N:21]([CH3:38])[C:22](=[O:30])[O:23][CH2:24][CH2:25][Si:26]([CH3:28])([CH3:29])[CH3:27])=[O:17])[CH2:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11345291rel-(1R,3S)-3-Benzoylcyclohexanecarboxylic acidHCID 59382944(S)-2-(trimethylsilyl)ethyl 2-amino-3-cyclohexylpropylcarbamate

Product 1

HCID 671917252-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexanecarboxamido)-3-cyclohexylpropylmethylcarbamateYield 94.6%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of cis-3-benzoylcyclohexane-1-carboxylic acid (78 mg, 0.34 mmol), 2-(trimethylsilyl)ethyl (S)-2-amino-3-cyclohexylpropylcarbamate (116 mg, 0.37 mmol) and diisopropylethylamine (0.13 mL, 0.70 mmol) in CH2Cl2 (2 mL) were added solid 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 200 mg, 0.53 mmol) and DMF (0.5 mL). The mixture was stirred at rt for 3 h, diluted with ether (90 mL), washed with 5% aqueous HCl (25 mL), sat'd aqueous NaHCO3 (25 mL), and brine (25 mL) and dried over Na2SO4. Removal of the solvent under reduced pressure left an oil (260 mg) which was applied to a 2-g silica SPE cartridge and eluted sequentially with 0, 10, 25, 50, 75, and 100% EtOAc in hexanes (15 mL of each) to give six fractions. Fractions 2-4 were pooled and evaporated to afford 2-(trimethylsilyl)ethyl (S)-2-(3-benzoylcyclohexane-carboxamido)-3-cyclohexylpropylmethylcarbamate (170 mg, 91%) as an oil. MS ESI+ve m/z 528 (M+1).

Workup

  1. washwashed with 5% aqueous HCl (25 mL)
  2. dry with materialdried over Na2SO4
  3. customRemoval of the solvent under reduced pressure
  4. waitleft an oil (260 mg) which
  5. washeluted sequentially with 0, 10, 25, 50, 75, and 100% EtOAc in hexanes (15 mL of each)
  6. customto give six fractions
  7. customevaporated

Sources & evidence

ORD record
ord-b4655aa62cbc49b6b9a3a97be4652fa6
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Linked notes

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