Ammonium Chloride → (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[hydroxy(4-hydroxymethyl-1-naphthyl)methyl]pyrrolidine

HRID 725947

Reaction equation

HRID 725947 reaction equation
[OH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](Br)=[CH:5][CH:4]=1.[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>O1CCCC1>[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]([OH:24])[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([CH2:2][OH:1])=[CH:4][CH:5]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 10969557tert-Butyl (2S,4R)-4-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 12749145(4-Bromonaphthalen-1-yl)methanol

Product 1

HCID 22881087(2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[hydroxy(4-hydroxymethyl-1-naphthyl)methyl]pyrrolidineYield 44%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-72 °C

Procedure

A solution of 4-hydroxymethyl-1-bromonaphthalene (3 g, 12.7 mmol) in tetrahydrofuran (50 ml) was added dropwise to a solution of 1.6M butyl lithium-hexane solution (20.6 ml, 32.9 mmol) in tetrahydrofuran (100 ml) at -72° C. in a nitrogen stream over 30 minutes. The resulting reaction solution was stirred at -72° C. for 30 minutes and a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (4.17 g, 12.7 mmol) in tetrahydrofuran (50 ml) was added dropwise over 10 minutes. Then, the reaction solution was stirred at -63° C. for 10 minutes. After addition of saturated aqueous ammonium chloride, the reaction solution was concentrated in vacuo. The resulting residue was poured into a liquid mixture of ethyl acetate with water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300 heptane-ethyl acetate 3:1→2:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[hydroxy(4-hydroxymethyl-1-naphthyl)methyl]pyrrolidine (2.71 g, yield: 44.0%) as a colorless oily substance.

Workup

  1. customThe resulting reaction solution
  2. stirringThen, the reaction solution was stirred at -63° C. for 10 minutes
  3. concentrationthe reaction solution was concentrated in vacuo
  4. additionThe resulting residue was poured into a liquid mixture of ethyl acetate with water
  5. washThe organic layer was washed with saturated aqueous sodium chloride
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3e4d674bf9c447c78e8fc76bb3e863f6
Source dataset
uspto-grants-1998_01
Patent number
US05707987

Linked notes

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