Diethyl Ether → trans-4-(2-Hydroxymethylphenyl)-1-methyl-2,3,4,4a,9,9a-hexahydro-1H-indeno[1,2-b]pyrazine

HRID 2164430Notes

Reaction equation

HRID 2164430 reaction equation
OCC1[CH:20]=[CH:19][CH:18]=[CH:17][C:4]=1[NH:5][C@@H:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][C@H:7]1[NH:15][CH3:16].Br[CH2:22][CH2:23]Br.C(N(CC)CC)C.[Br-].C([NH+](CC)CC)C.C([O:42][CH2:43][CH3:44])C>>[OH:42][CH2:43][C:44]1[CH:20]=[CH:19][CH:18]=[CH:17][C:4]=1[N:5]1[CH2:23][CH2:22][N:15]([CH3:16])[C@@H:7]2[CH2:8][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C@@H:6]12

Participants

6

Reactant 5

HCID 3283Diethyl EtherHCID 78391,2-Dibromoethane2×HCID 8471Triethylamine2×HCID 12493Triethylamine hydrobromideHCID 15807945trans-1-(2-Hydroxymethylanilino)-2-methylaminoindane

Product 1

HCID 86739971trans-4-(2-Hydroxymethylphenyl)-1-methyl-2,3,4,4a,9,9a-hexahydro-1H-indeno[1,2-b]pyrazineYield 54%

Procedure

A solution of trans 1-(2-hydroxymethylanilino)-2-methylaminoindane (1.16 kg; 4.3 moles) in 1,2-dibromoethane (7 l, 17.1 moles) and triethylamine (2.5 l; 34 moles) was added dropwise to stirred 1,2-dibromoethane (13 l; 31.9 moles) at ca. 100° over a period of 1.5h. This was followed by triethylamine (2.5 l; 34 moles) added dropwise over 30 min. The reaction was cooled to 50° and diethyl ether (80 l) was added with good stirring. After stirring for 1 h the precipitated triethylammonium bromide was filtered off and the resulting solution concentrated in vacuo to ca 3.5 l. Addition of ethyl acetate (2.5 l) assisted crystallisation of the required product. Filtration and trituration (pet. ether) afforded the title compound as a white crystalline solid (687 g; 54%) m.p. 166°-7°.

Workup

  1. additionadded dropwise over 30 min
  2. temperatureThe reaction was cooled to 50°
  3. filtrationwas filtered off
  4. concentrationthe resulting solution concentrated in vacuo to ca 3.5 l
  5. additionAddition of ethyl acetate (2.5 l)
  6. customcrystallisation of the required product
  7. filtrationFiltration and trituration (pet. ether)

Sources & evidence

ORD record
ord-76d4bb31244245f2a4584cff0d0961d7
Source dataset
uspto-grants-1985_03
Patent number
US04504480

Reaction notes

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