Diisopropylethylamine → methyl 4-[[[[(R)-1-[[4-(4-bromophenoxy)phenyl]methyl]-2-pyrrolidinyl]methyl]methylamino]methyl]benzoate

HRID 16526Notes

Reaction equation

HRID 16526 reaction equation
Cl.[CH3:2][N:3]([CH2:10][C:11]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][CH:12]=1)[CH2:4][CH:5]1[CH2:9][CH2:8][CH2:7][NH:6]1.[Br:21][C:22]1[CH:36]=[CH:35][C:25]([O:26][C:27]2[CH:34]=[CH:33][C:30]([CH:31]=O)=[CH:29][CH:28]=2)=[CH:24][CH:23]=1.C(N(C(C)C)CC)(C)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C>[Br:21][C:22]1[CH:36]=[CH:35][C:25]([O:26][C:27]2[CH:34]=[CH:33][C:30]([CH2:31][N:6]3[CH2:7][CH2:8][CH2:9][C@@H:5]3[CH2:4][N:3]([CH2:10][C:11]3[CH:12]=[CH:13][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:19][CH:20]=3)[CH3:2])=[CH:29][CH:28]=2)=[CH:24][CH:23]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 106362404-(4-Bromophenoxy)benzaldehydeHCID 68489053Methyl 4-[[methyl(2-pyrrolidinylmethyl)amino]methyl]benzoate hydrochloride salt

Product 1

HCID 68488973methyl 4-[[[[(R)-1-[[4-(4-bromophenoxy)phenyl]methyl]-2-pyrrolidinyl]methyl]methylamino]methyl]benzoateYield 94%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of methyl 4-[[methyl(2-pyrrolidinylmethyl)amino]methyl]benzoate hydrochloride salt (310 mg, 1.04 mmol) and 4-(4-bromophenoxy)benzaldehyde (301 mg, 1.1 mmol) in dichloroethane was stirred as diisopropylethylamine (DIEA, 1 mL) and sodium triacetoxyborohydride (286 mg, 1.35 mmol) were added sequentially at ambient temperature. After stirring at ambient temperature for 17 hours, the reaction mixture was treated with a saturated aqueous solution of sodium bicarbonate and extracted with EtOAc. The combined organic layers were dried and concentrated. Purification by flash chromatography afforded methyl 4-[[[[(R)-1-[[4-(4-bromophenoxy)phenyl]methyl]-2-pyrrolidinyl]methyl]methylamino]methyl]benzoate (510 mg, 94%); 1NMR (400 MHz, DMSO-d6) δ 7.98 (d, 2H), 7.42 (dd, 2H), 7.24 (d, 2H), 6.91 (d, 2H), 6.83 (d, 2H), 3.82 (s, 3H), 4.16 (d, 1H), 3.55 (dd, 2H), 3.23 (d, 1H), 2.90 (m, 1H), 2.42 (m, 1H), 2.55 (dd, 1H), 2.38 (dd, 1H), 2.11 (s, 3H), 2.17 (m, 1H), 1.99 (m, 1H), 1.63 (m, 3H) ppm.

Workup

  1. additionwere added sequentially at ambient temperature
  2. extractionextracted with EtOAc
  3. customThe combined organic layers were dried
  4. concentrationconcentrated
  5. customPurification by flash chromatography

Sources & evidence

ORD record
ord-dc8e964846f740398d8c97ccd44fe20e
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Reaction notes

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