1,2-Dichloroethane → ethyl 1-[(R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate

HRID 333445Notes

Reaction equation

HRID 333445 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH:36]1([C:42]2([C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]2)[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1.C(N(CC)CC)C.[OH-].[Na+]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=1)[C:10]([N:45]1[CH2:46][CH2:47][C:42]([CH:36]2[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]2)([C:48]([O:50][CH2:51][CH3:52])=[O:49])[CH2:43][CH2:44]1)=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 7017908Boc-O-methyl-D-tyrosineHCID 18418945Ethyl 4-cyclohexyl-4-piperidinecarboxylate

Product 1

HCID 66987792ethyl 1-[(R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylateYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 3.22 g (10.9 mmol) of (R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)-propionic acid dissolved in 20 mL of DMF are added 2.29 g (12.0 mmol) of EDC, 1.62 g (12.0 mmol) of HOBt, 2.62 g (10.9 mmol) of ethyl 4-cyclohexylpiperidine-4-carboxylate (cf. preparation 3-1-2) and 4.6 mL (32.7 mmol) of triethylamine. After stirring for 2 hours 30 minutes, the reaction is stopped by adding aqueous 1N sodium hydroxide solution and the organic products are extracted with dichloromethane. The organic phase is dried over MgSO4, filtered and evaporated. The crude product obtained is chromatographed on silica gel (eluent: 7/3 heptane/EtOAc). 3.70 g of ethyl 1-[(R)-2-tert-butoxycarbonylamino-3-(4-methoxyphenyl)propionyl]-4-cyclohexyl-piperidine-4-carboxylate in the form of a white powder are obtained in a yield of 66%.

Workup

  1. extractionthe organic products are extracted with dichloromethane
  2. dry with materialThe organic phase is dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product obtained
  6. customis chromatographed on silica gel (eluent: 7/3 heptane/EtOAc)

Sources & evidence

ORD record
ord-5d363eeaa04142e29dc00e35def5544e
Source dataset
uspto-grants-2014_11
Patent number
US08877968B2

Reaction notes

Loading…