Ammonium Chloride → Tert-butyl (3s,5s,6r)-3-allyl-2-oxo-5,6-diphenyl-3-[1-(2-trimethylsilanyl-ethoxycarbonyl)piperidin-4-ylmethyl]morpholine-4-carboxylate

HRID 1743267Notes

Reaction equation

HRID 1743267 reaction equation
[CH2:1]([C@H:4]1[C:9](=[O:10])[O:8][C@H:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@H:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:5]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:2]=[CH2:3].C1OCCOCCOCCOCCOC1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:56][CH:57]1[CH2:62][CH2:61][N:60]([C:63]([O:65][CH2:66][CH2:67][Si:68]([CH3:71])([CH3:70])[CH3:69])=[O:64])[CH2:59][CH2:58]1.[Cl-].[NH4+]>C1COCC1>[CH2:1]([C@:4]1([CH2:56][CH:57]2[CH2:62][CH2:61][N:60]([C:63]([O:65][CH2:66][CH2:67][Si:68]([CH3:69])([CH3:71])[CH3:70])=[O:64])[CH2:59][CH2:58]2)[C:9](=[O:10])[O:8][C@H:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C@H:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:5]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH:2]=[CH2:3]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 3633615-Crown-5HCID 2724254Sodium bis(trimethylsilyl)amideHCID 11058313Tert-butyl (3s,5s,6r)-3-allyl-2-oxo-5,6-diphenylmorpholine-4-carboxylateHCID 222383942-Trimethylsilanylethyl 4-bromomethyl-piperidine-1-carboxylate

Product 1

HCID 91566876Tert-butyl (3s,5s,6r)-3-allyl-2-oxo-5,6-diphenyl-3-[1-(2-trimethylsilanyl-ethoxycarbonyl)piperidin-4-ylmethyl]morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

4.9 g of tert-butyl (3S,5S,6R)-3-allyl-2-oxo-5,6-diphenylmorpholine-4-carboxylate were dissolved in 100 ml of THF. 14.9 ml of 15-crown-5 were added, and the mixture was cooled to −78° C. Then 6.8 ml of a 2 M solution of NaHMDS in THF were added dropwise. The mixture was stirred for 10 min and then 8 g of 2-trimethylsilanylethyl 4-bromomethylpiperidine-1-carboxylate were added dropwise. The mixture was allowed to warm to 0° C. over the course of 6 h, and the reaction was then stopped by adding 500 ml of saturated ammonium chloride solution. The aqueous phase was extracted 3 times with 400 ml of ethyl acetate each time, and the combined organic phases were dried with MgSO4. The solvents were removed in vacuo, and the residue was chromatographed on silica gel.

Workup

  1. temperatureto warm to 0° C. over the course of 6 h
  2. extractionThe aqueous phase was extracted 3 times with 400 ml of ethyl acetate each time
  3. dry with materialthe combined organic phases were dried with MgSO4
  4. customThe solvents were removed in vacuo
  5. customthe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-c763f98885134e59bb54f39f86b5311f
Source dataset
uspto-grants-2006_03
Patent number
US07008957B2

Reaction notes

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