Hydrochloric Acid → Hydrochloric Acid

HRID 2395828

Reaction equation

HRID 2395828 reaction equation
C([Cl:5])(=O)CC.[CH3:6][O:7][CH2:8][C:9]1([N:22]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:23](=[O:26])[CH2:24][CH3:25])[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)[CH2:11][CH2:10]1.S1C=CC=C1CCN1CCC(NC2C=CC=CC=2)(COC)CC1.[ClH:56]>CCOCC.C(N(CC)CC)C.C(Cl)Cl>[ClH:5].[CH3:25][CH2:24][C:23]([N:22]([C:9]1([CH2:8][O:7][CH3:6])[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)[CH2:13][CH2:14]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:26].[ClH:56]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid2×HCID 41693Sufentanil2×HCID 62324Propionyl chlorideHCID 152954984-(Methoxymethyl)-N-phenyl-1-[2-(2-thienyl)ethyl]-4-piperidinamine2×

Product 2

HCID 313Hydrochloric AcidHCID 18463211164790-60-7

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

Propionyl chloride (1.3 equivalents) was added to a 0.4M methylene chloride solution of 6 in a glass stoppered RB flask at RT. A mild exotherm developed and analysis by LC at the end of 40 minutes showed 90% sufentanil 7 with about 7% starting material 6. About 8% by weight of triethylamine was then added and stirred for another 40 minutes at RT. LC showed 95% product with no trace of starting material 6. The mixture was then quenched with an excess of dilute ammonium hydroxide and the lower methylene chloride layer was separated, washed with water and dried. Evaporation of methylene chloride gave a yellow powder which by LC amounted to 95% sufentanil 7. This was converted to HCl salt by dissolving in ether (250 ml) and stirring with 4N HCl [100 ml]. The precipitated HCl salt was filtered off, washed with ether and air-dried. Recrystallization from water (6 ml for every gm of Sufentanil.HCl) gave sufentanil HCl (19.6 g) as white paste with LC purity of 99.50%. The isolated yield of the pure HCl salt was 85%. H1NMR (CDCl3): δ7.25-6.85 (m,8H), 4.05 (s,2H), 3.35 (s,3H), 3.14-1.56 (m,14H), 0.95 (t,3H).

Workup

  1. customat RT
  2. customat the end of 40 minutes
  3. customThe mixture was then quenched with an excess of dilute ammonium hydroxide
  4. customthe lower methylene chloride layer was separated
  5. washwashed with water
  6. customdried
  7. customEvaporation of methylene chloride
  8. customgave a yellow powder which by LC
  9. filtrationThe precipitated HCl salt was filtered off
  10. washwashed with ether
  11. customair-dried
  12. customRecrystallization from water (6 ml for every gm of Sufentanil

Sources & evidence

ORD record
ord-94076dbe99b148209ca5db418832a78b
Source dataset
uspto-grants-1996_02
Patent number
US05489689

Linked notes

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