Trifluoroacetic acid → methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate

HRID 452014Notes

Reaction equation

HRID 452014 reaction equation
[NH2:1][C@@H:2]([CH2:15][C@H:16]1[CH2:21][CH2:20][CH2:19][O:18][CH2:17]1)[CH2:3][N:4]([CH3:14])[C:5](=[O:13])[O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.C1N=CN([C:36]([N:38]2[CH:42]=N[CH:40]=[CH:39]2)=[O:37])C=1.[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2CCCN[CH2:60]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:43][C:44]1[CH:45]=[C:46]([C@@H:50]([C@@H:59]2[CH2:60][CH2:40][CH2:39][N:38]([C:36](=[O:37])[NH:1][C@@H:2]([CH2:15][C@H:16]3[CH2:21][CH2:20][CH2:19][O:18][CH2:17]3)[CH2:3][N:4]([C:5]([O:6][CH2:7][CH2:8][Si:9]([CH3:12])([CH3:11])[CH3:10])=[O:13])[CH3:14])[CH2:42]2)[O:51][CH2:52][CH2:53][NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:47]=[CH:48][CH:49]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 580174332-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamateHCID 59598478Carbamic acid,N-[2-[(R)-(3-chlorophenyl)(3R)-3-piperidinylmethoxy]ethyl]-,methyl ester

Product 1

HCID 67363897methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamateYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

At 0° C., to a solution of 2-(trimethylsilyl)ethyl (S)-2-amino-3-((R)-tetrahydro-2H-pyran-3-yl)propyl(methyl)carbamate (1.9 g, 6 mmol) and DIPEA (3.87 g, 30 mmol) in anhydrous CH2Cl2 (20 mL) was added CDI (1.26 g, 7.8 mmol). After addition, the mixture was stirred for 1 hr at 0° C., followed by addition of methyl 2-((R)-(3-chlorophenyl)((R)-piperidin-3-yl)methoxy)ethylcarbamate as TFA salt (2.8 g, 6.6 mmol) in anhydrous CH2Cl2 (20 mL). The reaction mixture was allowed to warm to rt and stirred overnight. After the reaction was completed, the solvent was removed in vacuo. The product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1) to afford methyl 2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(N-Methyl-2-(trimethylsilyl)ethoxycarbonylamino)-3-((R)-tetrahydro-2H-pyran-3-yl)propan-2-ylcarbamoyl)piperidin-3-yl)methoxy)ethylcarbamate (3.0 g, 75% yield).

Workup

  1. additionAfter addition
  2. temperatureto warm to rt
  3. stirringstirred overnight
  4. customthe solvent was removed in vacuo
  5. customThe product was purified by column chromatography on silica gel eluting with petroleum ether/EtOAc (5:1→2:1)

Sources & evidence

ORD record
ord-f398c4f705944c6ba50f2a3fdcfa6927
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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