Ammonium Chloride → 10-Hydroxy-10-(4-ethoxybutyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole

HRID 2231822Notes

Reaction equation

HRID 2231822 reaction equation
[Mg].Br[CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH2:8][CH3:9].[N:10]1[CH2:11][CH2:12][CH2:13][N:14]2[C:22]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:16](=[O:23])[C:15]=12.[Cl-].[NH4+]>BrCCCCOCC.CCOCC.ClCCCl>[OH:23][C:16]1([CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH2:8][CH3:9])[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=2[N:14]2[CH2:13][CH2:12][CH2:11][N:10]=[C:15]12

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 64275731-Bromo-4-ethoxybutaneHCID 141813833,4-Dihydropyrimido(1,2-a)indol-10(2h)-one

Product 1

HCID 1418139910-Hydroxy-10-(4-ethoxybutyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole

Reagents, catalysts & solvents 3

HCID 64275731-Bromo-4-ethoxybutaneCatalystHCID 111,2-DichloroethaneSolventHCID 3283Diethyl EtherSolvent2×

Procedure

Ether (10 ml) and a few drops 4-bromo-1-ethoxybutane were added to magnesium turnings (1.46 g). After the reaction started, the remainder of the 4-bromo-1-ethoxybutane (total 10.86 g) in ether (50 ml) was added dropwise over 20 minutes. The mixture was stirred under argon at room temperature for 30 minutes, cooled to 0° C. over 30 minutes and 3,4-dihydropyrimido[1,2-a]indol-10(2H)-one (3.72 g) in dry 1,2-dichloroethane (20 ml) added dropwise over 20 minutes. The solution was stirred under argon at 0° C. for 1 hour, poured onto a swirling mixture of ice (100 ml) and saturated aqueous ammonium chloride (60 ml), and the mixture stirred for a further 20 minutes. The mixture was concentrated in vacuo and the aqueous residue extracted with chloroform (3×100 ml). The extracts were dried (Na2SO4) and concentrated in vacuo. Ether (20 ml) was added and the product was filtered and recrystallised from ethyl acetate to give the title compound as the free base (2.99 g), m.p. 123°-124° C. The free base was acidified with ethereal HCl to give the title compound as the hydrochloride, m.p. 189°-190° C.

Workup

  1. temperaturecooled to 0° C. over 30 minutes
  2. stirringThe solution was stirred under argon at 0° C. for 1 hour
  3. stirringthe mixture stirred for a further 20 minutes
  4. concentrationThe mixture was concentrated in vacuo
  5. extractionthe aqueous residue extracted with chloroform (3×100 ml)
  6. dry with materialThe extracts were dried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. additionEther (20 ml) was added
  9. filtrationthe product was filtered
  10. customrecrystallised from ethyl acetate

Sources & evidence

ORD record
ord-7dcab2ac2f37442f9f3639a0f2d9320c
Source dataset
uspto-grants-1988_11
Patent number
US04784996

Reaction notes

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