Propargyl chloroformate → HCID 10393852, compound

HRID 1727166Notes

Reaction equation

HRID 1727166 reaction equation
[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:33])[CH3:32])[CH2:25][CH2:26][CH:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[CH:20]4[OH:35])=[O:17])[CH2:15][C@@:7]3([OH:36])[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:38]([O:40][CH2:41][C:42]#[CH:43])=[O:39]>CN(C)C1C=CN=CC=1.ClCCl>[Cl:1][C:2]1[C:11]2[N:10]([CH3:12])[O:9][C@H:8]3[NH:13][C@H:14]([C:16]([O:18][C@@H:19]4[C@:28]5([OH:29])[C@@H:23]([C@H:24]([CH:31]([CH3:32])[CH3:33])[CH2:25][CH2:26][C@H:27]5[CH3:30])[CH:22]=[C:21]([CH3:34])[C@H:20]4[O:35][C:38]([O:40][CH2:41][C:42]#[CH:43])=[O:39])=[O:17])[CH2:15][C@@:7]3([OH:36])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 3356829Propargyl chloroformateHCID 86614040HCID 86614040, compound

Product 1

HCID 10393852HCID 10393852, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To (1S,4aS,5S,8aR)-2,8a-dihydroxy-3,8-dimethyl-5-(1-methylethyl)-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl (2S,3aR,9bR)-6-chloro-9b-hydroxy-5-methyl-1,2,3,3a,5,9b-hexahydropyrrolo[2,3-c][2,1]benzoxazine-2-carboxylate (Preparation 144, 500 mg, 0.96 mmol) and 4-dimethylaminopyridine (350 mg, 2.9 mmol) in dichloromethane (25 ml) at 0° C. under nitrogen was added propargyl chloroformate (170 mg, 1.44 mmol) and the resulting mixture stirred at 0° C. for 30 minutes and at room temperature for 3 hours. The reaction mixture was diluted with dichloromethane (100 ml) and washed with citric acid solution (3×50 ml) and water (2×50 ml), dried (MgSO4) and concentrated in vacuo to give a solid. The crude product was purified by flash chromatography on silica (40 g) eluting with hexane:ethyl acetate (3:2). The pure fractions were combined and concentrated in vacuo to give the title product (462 mg, 80%).

Workup

  1. washwashed with citric acid solution (3×50 ml) and water (2×50 ml)
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. customto give a solid
  5. customThe crude product was purified by flash chromatography on silica (40 g)
  6. washeluting with hexane:ethyl acetate (3:2)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7d182ceea87443a6b4e4ef8f7c4b53d9
Source dataset
uspto-grants-2009_02
Patent number
US07494992B2

Reaction notes

Loading…