Sodium borohydride → cis-5-Propyl-4,5,6,7-tetrahydro-1-benzothiophen-4-amine

HRID 1824128Notes

Reaction equation

HRID 1824128 reaction equation
[BH4-].[Na+].[CH2:3]([CH:6]1[CH2:7][CH2:8][C:9]2[S:13][CH:12]=[CH:11][C:10]=2/[C:14]/1=[N:15]\[OH:16])[CH2:4][CH3:5]>COCCOC.[Ti](Cl)(Cl)(Cl)Cl>[OH-:16].[NH4+:15].[CH2:3]([C@@H:6]1[C@H:14]([NH2:15])[C:10]2[CH:11]=[CH:12][S:13][C:9]=2[CH2:8][CH2:7]1)[CH2:4][CH3:5]

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 58583494(NZ)-N-(5-propyl-6,7-dihydro-5H-1-benzothiophen-4-ylidene)hydroxylamine

Product 2

HCID 14923Ammonium HydroxideYield 0.5%HCID 58583416cis-5-Propyl-4,5,6,7-tetrahydro-1-benzothiophen-4-amineYield 75.4%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of sodium borohydride (4.63 g) in ethylene glycol dimethyl ether (150 ml) at 0° C. under N2 was added titanium tetrachloride (6.89 ml). After 5 min, (4Z)-5-propyl-6,7-dihydro-1-benzothiophen-4(5H)-one oxime (6.25 g) in 50 ml of ethylene glycol dimethyl ether was added dropwise to a blue solution. The reaction mixture was stirred at ambient temperate for 24 h and carefully quenched at 0° C. with 2 N NaOH. The aqueous layer was extracted with methylene chloride (3×200 ml), dried MgSO4, filtered and concentrated. MPLC chromatography on a biotage 40 L column with 2–4% methanol/methylene chloride with 0.5% ammonium hydroxide provided Cis-5-propyl-4,5,6,7-tetrahydro-1-benzothiophen-4-amine (2.2 g): 1H NMR (300 MHz, CDCl3) δ) 7.10, 6.96, 3.92, 2.90–2.72, 1.72, 1.47–1.36, 0.98; HRMS (FAB) calcd for C11H17NS+H 196.1160, found 196.1164. and trans-5-propyl-4,5,6,7-tetrahydro-1-benzothiophen-4-amine (2.68 g) as an oil: 1H NMR (300 MHz, CDCl3) δ) 7.10, 7.02, 3.59, 2.78, 2.07, 1.66–1.48, 1.38–1.24, 0.96; HRMS (FAB) calcd for C11H17NS+H 196.1160, found 196.1157.

Workup

  1. customcarefully quenched at 0° C. with 2 N NaOH
  2. extractionThe aqueous layer was extracted with methylene chloride (3×200 ml), dried MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-1fd3aa65ed254756b3570fe47e6d6155
Source dataset
uspto-grants-2006_05
Patent number
US07041672B2

Reaction notes

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