Isopropyl Acetate → methyl (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride

HRID 1747141Notes

Reaction equation

HRID 1747141 reaction equation
[C@H:1]12[CH2:7][C@H]([CH:5]=[CH:6]1)C(=O)[NH:2]2.S(Cl)([Cl:11])=O.[C:13]([O:16][CH:17](C)C)(=[O:15])[CH3:14]>CO>[ClH:11].[NH2:2][C@H:1]1[CH2:7][C@@H:14]([C:13]([O:16][CH3:17])=[O:15])[CH:5]=[CH:6]1

Participants

5

Reactant 3

HCID 7915Isopropyl AcetateHCID 24386Thionyl ChlorideHCID 11789150(+)-Vince lactam

Product 1

HCID 12899910methyl (1R,4S)-4-aminocyclopent-2-ene-1-carboxylate hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
8 °C

Procedure

A solution of (1S,4R)-2-azabicyclo[2.2.1]hept-5-en-3-one (725 g, 6.64 mol) in MeOH (2.2 L) was stirred in an ice bath to 0° C. Thionyl chloride (290 mL, 3.99 mol) was added dropwise over a 2.25 h period while keeping the temperature below 13° C. The reaction was stirred for 2 h at 8° C. Isopropyl acetate (16.3 L) was added and the slurry stirred for 1 h. The solid was filtered with a Buchner funnel, washed with isopropylacetate (˜1 L) and the solid was allowed to air-dry overnight to afford an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.44 (br. s., 3H), 5.99-6.16 (m, 1H), 5.90 (dt, J=2.4, 5.3 Hz, 1H), 4.17 (br. s., 1H), 3.56-3.79 (m, 4H), 2.56 (m, 1H), 1.84-2.04 (m, 1H).

Workup

  1. customthe temperature below 13° C
  2. stirringthe slurry stirred for 1 h
  3. filtrationThe solid was filtered with a Buchner funnel
  4. washwashed with isopropylacetate (˜1 L)
  5. customto air-dry overnight
  6. customto afford an off-white solid

Sources & evidence

ORD record
ord-7303ea7e45ab4d3ba65f9aa13cb2ed0f
Source dataset
uspto-grants-2015_10
Patent number
US09150532B2

Reaction notes

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