Triethylamine → 3-(RS)-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-ylmethyl]-4-(SR)-phenylpyrrolidine-1-carboxylic Acid Tert-Butyl Ester

HRID 1182161Notes

Reaction equation

HRID 1182161 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]([CH:19]=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[Br:22][C:23]1[CH:40]=[CH:39][C:26]([CH2:27][N:28]2[CH2:32][CH2:31][C:30]3([CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)[C:29]2=[O:38])=[CH:25][CH:24]=1.C(N(CC)CC)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:10]([CH2:19][N:35]2[CH2:34][CH2:33][C:30]3([C:29](=[O:38])[N:28]([CH2:27][C:26]4[CH:25]=[CH:24][C:23]([Br:22])=[CH:40][CH:39]=4)[CH2:32][CH2:31]3)[CH2:37][CH2:36]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 2724942TriacetoxyborohydrideHCID 450741072,8-Diazaspiro[4.5]decan-1-one, 2-[(4-bromophenyl)methyl]-, (Hydrochloride) (1:1)HCID 724802973-(RS)-formyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 673694643-(RS)-[2-(4-Bromobenzyl)-1-oxo-2,8-diaza-spiro[4.5]dec-8-ylmethyl]-4-(SR)-phenylpyrrolidine-1-carboxylic Acid Tert-Butyl EsterYield 89.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 275.3 mg (1 mmol) of 3-(RS)-formyl-4-(SR)-phenylpyrrolidine-1-carboxylic acid tert-butyl ester and 359.1 mg (1 mmol) of 2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one hydrochloride were added 20 mL of DCE and 139 μL (1 mmol) of triethylamine. The reaction mixture was agitated for 10 minutes at room temperature before adding 334 mg (1.5 mmol) of triacetoxyborohydride. After an overnight agitation, 10 mL of saturated solution of sodium bicarbonate were added and the solution was extracted with DCM. The organic layers were dried over sodium sulfate, filtered and evaporated in vacuo. The crude yellow oil was purified by flash chromatography on silica gel (DCM/methanol 0% to 2%) giving Compound 1 as a colorless solid (520 mg, 89.3%).

Workup

  1. extractionthe solution was extracted with DCM
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude yellow oil was purified by flash chromatography on silica gel (DCM/methanol 0% to 2%)

Sources & evidence

ORD record
ord-b5d633ae83074b05bafe19ab8098a007
Source dataset
uspto-grants-2007_10
Patent number
US07288548B2

Reaction notes

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