1,2-Dichloroethane → 8-(1-Benzyl-4-(SR)-phenylpyrrolidin-3-(RS)-ylmethyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one dihydrochloride

HRID 1182163Notes

Reaction equation

HRID 1182163 reaction equation
[Br:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C:9]3([CH2:16][CH2:15][N:14]([CH2:17][CH:18]4[CH:22]([C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH2:21][NH:20][CH2:19]4)[CH2:13][CH2:12]3)[C:8]2=[O:29])=[CH:4][CH:3]=1.[CH:32](=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Cl:53]CCCl>>[ClH:53].[ClH:53].[CH2:32]([N:20]1[CH2:21][CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:18]([CH2:17][N:14]2[CH2:13][CH2:12][C:9]3([C:8](=[O:29])[N:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([Br:1])=[CH:31][CH:30]=4)[CH2:11][CH2:10]3)[CH2:16][CH2:15]2)[CH2:19]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

5

Reactant 4

HCID 111,2-DichloroethaneHCID 240BenzaldehydeHCID 2724942TriacetoxyborohydrideHCID 673687102-(4-Bromobenzyl)-8-(4-(SR)-phenylpyrrolidin-3-(RS)-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one

Product 1

HCID 673706578-(1-Benzyl-4-(SR)-phenylpyrrolidin-3-(RS)-ylmethyl)-2-(4-bromobenzyl)-2,8-diaza-spiro[4.5]decan-1-one dihydrochlorideYield 39.5%

Procedure

A solution of 28.9 mg (60 μmol) of 2-(4-bromobenzyl)-8-(4-(SR)-phenylpyrrolidin-3-(RS)-ylmethyl)-2,8-diaza-spiro[4.5]decan-1-one and 6.3 mg (60 μmol) of benzaldehyde in 1.5 mL of DCE was agitated for 10 minutes at room temperature before adding 20 mg (90 μmol) of triacetoxyborohydride. The reaction mixture was then stirred overnight and quenched with a saturated solution of sodium bicarbonate (1 mL). The solution was extracted with DCM (2×2 mL) and the combined organic layers were concentrated. The crude was purified by semi-preparative HPLC (method B) yielding 15.3 mg (39.5%) of Compound 98 as a pale yellow solid.

Workup

  1. customquenched with a saturated solution of sodium bicarbonate (1 mL)
  2. extractionThe solution was extracted with DCM (2×2 mL)
  3. concentrationthe combined organic layers were concentrated
  4. customThe crude was purified by semi-preparative HPLC (method B)

Sources & evidence

ORD record
ord-ed32c18d5b334a5db57a0406aea0b13e
Source dataset
uspto-grants-2007_10
Patent number
US07288548B2

Reaction notes

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