Diisopropylethylamine → tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamate

HRID 2355501Notes

Reaction equation

HRID 2355501 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1.[N+](C1C=CC([O:29][C:30]([NH:32][CH2:33][C@@H:34]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[CH2:35][CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)=O)=CC=1)([O-])=O.CCN(C(C)C)C(C)C>CC#N.C(Cl)Cl.CCOCC>[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:30]([NH:32][CH2:33][C@@H:34]([NH:42][C:43](=[O:49])[O:44][C:45]([CH3:47])([CH3:46])[CH3:48])[CH2:35][CH:36]3[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41]3)=[O:29])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH3:14])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 59382814(S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-olHCID 59382967(S)-4-nitrophenyl 2-(t-butoxycarbonylamino)-3-cyclohexylpropylcarbamate

Product 1

HCID 86626201tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamateYield 49%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (S)-1-(3-chlorophenyl)-5-methoxy-1-((R)-piperidin-3-yl)pentan-1-ol (31 mg, 0.10 mmol) and (S)-tert-butyl 1-(p-nitrophenoxycarbonylamino)-3-cyclohexylpropan-2-ylcarbamate (40 mg, 0.10 mmol) in MeCN (1 mL) and CH2Cl2 (1 mL) was added DIEA (50 μL, 0.28 mmol). The mixture was stirred at rt for 20 h, diluted with ether (90 mL), washed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL) and dried over MgSO4. Removal of the solvent left an oil (82 mg) which was applied to a 2-g silica SPE cartridge which was eluted sequentially with 10, 25, 50, 75 and 100% ethyl acetate in hexanes (15 mL of each) to afford 5 fractions. The 4th fraction was concentrated to afford tert-butyl (S)-1-((R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxamido)-3-cyclohexylpropan-2-ylcarbamate (29 mg, 49%) as an oil.

Workup

  1. washwashed with 5% aq HCl (20 mL) and 1 M aq NaOH (20 mL)
  2. dry with materialdried over MgSO4
  3. customRemoval of the solvent
  4. waitleft an oil (82 mg) which
  5. washwas eluted sequentially with 10, 25, 50, 75 and 100% ethyl acetate in hexanes (15 mL of each)
  6. customto afford 5 fractions
  7. concentrationThe 4th fraction was concentrated

Sources & evidence

ORD record
ord-b00ae3725b954e89b83cb808821d4e82
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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