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

HRID 630362Notes

Reaction equation

HRID 630362 reaction equation
Cl.[Br:2][C:3]1[CH:24]=[CH:23][C:6]([O:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH3:22])[CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][NH:18]3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.[CH:25]([C:27]1[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=1)=O.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:2][C:3]1[CH:4]=[CH:5][C:6]([O:7][C:8]2[CH:9]=[CH:10][C:11]([CH2:14][N:15]([CH2:16][C@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3[CH2:25][C:27]3[CH:36]=[CH:35][C:30]([C:31]([O:33][CH3:34])=[O:32])=[CH:29][CH:28]=3)[CH3:22])=[CH:12][CH:13]=2)=[CH:23][CH:24]=1

Participants

7

Reactant 5

HCID 15294Methyl 4-FormylbenzoateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 68490308HCID 68490308, compound

Product 1

HCID 68484662methyl 4-[[(R)-2-[[[[4-(4-bromophenoxy)phenyl]methyl]methylamino]methyl]-1-pyrrolidinyl]methyl]benzoateYield 86%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of (R)—N—[[4-(4-bromophenoxy)phenyl]methyl]-N-methyl-2-pyrrolidinemethanamine hydrochloride salt (0.87 g, 2 mmol) and methyl 4-formylbenzoate (346 mg, 2.11 mmol) in dichloroethane (20 mL) was stirred as diisopropylethylamine (0.12 mL, 3 mmol) and sodium triacetoxyborohydride (536 mg, 2.53 mmol) were added sequentially. The reaction was stirred at ambient temperature overnight. The reaction was treated with a saturated aqueous solution of sodium bicarbonate and extracted with ethyl acetate (2×). The combined organic extracts were dried and concentrated. Purification by flash chromatography on silica gel gave 0.9 g of methyl 4-[[(R)-2-[[[[4-(4-bromophenoxy)phenyl]methyl]methylamino]methyl]-1-pyrrolidinyl]methyl]benzoate.

Workup

  1. additionwere added sequentially
  2. extractionextracted with ethyl acetate (2×)
  3. customThe combined organic extracts were dried
  4. concentrationconcentrated
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-24d1df246f434992989077c220a5e3a2
Source dataset
uspto-grants-2016_04
Patent number
US09315509B2

Reaction notes

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