Triphenylphosphine → 1-acetyl-6-bromo-2,3-dihydro-5-(1-methyl-1,2,3,6-tetrahydropyridin-4-ylmethoxy)-1H-indole

HRID 1741036Notes

Reaction equation

HRID 1741036 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([OH:14])=[C:10]([Br:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:34][N:35]1[CH2:40][CH:39]=[C:38]([CH2:41]O)[CH2:37][CH2:36]1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][C:9]([O:14][CH2:41][C:38]3[CH2:39][CH2:40][N:35]([CH3:34])[CH2:36][CH:37]=3)=[C:10]([Br:13])[CH:11]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 1189211,2,3,6-Tetrahydro-1-methylpyridine-4-methanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 219483801-(6-Bromo-5-hydroxy-2,3-dihydro-1H-indol-1-yl)ethan-1-one

Product 1

HCID 107850361-acetyl-6-bromo-2,3-dihydro-5-(1-methyl-1,2,3,6-tetrahydropyridin-4-ylmethoxy)-1H-indoleYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
32 °C

Procedure

A stirred suspension of powdered 1-acetyl-6-bromo-2,3-dihydro-1H-indol-5-ol (Tetrahedron, 1973, 29(8), 1115) (19 g, 0.074 mole) in dry THF (1700 ml) at room temp. under argon was treated with triphenylphosphine (19.6 g, 0.075 mole) and 1-methyl-1,2,3,6-tetrahydropyridine-4-methanol (J. Med. Chem., 1988, 31, 545) (9.5 g, 0.075 mole), followed by the dropwise addition over 15 mins. of a solution of diethyl azodicarboxylate (11.8 ml, 0.075 mole) in THF (40 ml). A mild exotherm occured and the insoluble material dissolved. The solution was warmed at 32° C. for 1 hour, then concentrated in vacuo to approx. 500 ml volume. The solid which had formed was filtered off and dried according 16.1 g of beige solid. The filtrate was concentrated in vacuo and the residue treated with ethyl acetate (700 ml) and 1M HCl acid (500 ml), shaken well and the acid layer separated. This was washed with ethyl acetate, then basified with 40% NaOH and extracted with ethyl acetate, followed by chloroform. The combined extracts were dried (Na2SO4) and concentrated in vacuo to leave a yellow solid, which was recrystallised from ethyl acetate (3.8 g) giving a total yield of 19.9 g (74%) of 1-acetyl-6-bromo-2,3-dihydro-5-(1-methyl-1,2,3,6-tetrahydropyridin-4-ylmethoxy)-1H-indole.

Workup

  1. additionfollowed by the dropwise addition over 15 mins
  2. dissolutionthe insoluble material dissolved
  3. concentrationconcentrated in vacuo to approx. 500 ml volume
  4. customThe solid which had formed
  5. filtrationwas filtered off
  6. customdried
  7. concentrationThe filtrate was concentrated in vacuo
  8. additionthe residue treated with ethyl acetate (700 ml) and 1M HCl acid (500 ml)
  9. customthe acid layer separated
  10. washThis was washed with ethyl acetate
  11. extractionextracted with ethyl acetate
  12. dry with materialThe combined extracts were dried (Na2SO4)
  13. concentrationconcentrated in vacuo
  14. customto leave a yellow solid, which
  15. customwas recrystallised from ethyl acetate (3.8 g)

Sources & evidence

ORD record
ord-f558a22254f14d84b99cc21c1f6d5bb5
Source dataset
uspto-grants-1999_10
Patent number
US05972951

Reaction notes

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