Cyanomethylenetributylphosphorane → Benzyl 9a-methyl-3-((S)-3-methyl-1-oxoisochroman-6-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

HRID 2175786Notes

Reaction equation

HRID 2175786 reaction equation
O[CH:2]([C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[O:28][C@@H:27]([CH3:34])[CH2:26]2)[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:6][C:5]1([CH2:21][OH:22])[CH3:20].C(C=P(CCCC)(CCCC)CCCC)#N>C1C=CC=CC=1>[CH3:20][C:5]12[CH2:6][N:7]([C:10]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)=[O:11])[CH2:8][CH2:9][N:4]1[CH2:3][CH:2]([C:23]1[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[O:28][C@@H:27]([CH3:34])[CH2:26]3)[O:22][CH2:21]2

Participants

4

Reactant 2

HCID 4622928CyanomethylenetributylphosphoraneHCID 86727035benzyl 4-(2-hydroxy-2-((S)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)-3-methylpiperazine-1-carboxylate

Product 1

HCID 86727034Benzyl 9a-methyl-3-((S)-3-methyl-1-oxoisochroman-6-yl)hexahydropyrazino[2,1-c][1,4]oxazine-8(1H)-carboxylate

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
135 °C

Procedure

The mixture of benzyl 4-(2-hydroxy-2-((S)-3-methyl-1-oxoisochroman-6-yl)ethyl)-3-(hydroxymethyl)-3-methylpiperazine-1-carboxylate (762 mg, 1.60 mmol) and cyanomethylenetributylphosphorane (471 mg, 1.90 mmol) in dry benzene was degassed and heated to 135° C. in a microwave reactor for 3.5 h. After which point, the reaction mixture was cooled down to rt, concentrated to dryness and purified on silica gel to afford the title compound (cis or trans): MS: m/e 451.2 (M+H)+.

Workup

  1. customwas degassed
  2. temperatureAfter which point, the reaction mixture was cooled down to rt
  3. concentrationconcentrated to dryness
  4. custompurified on silica gel

Sources & evidence

ORD record
ord-b049ce2e143a4fde907573ba5585dd99
Source dataset
uspto-grants-2015_06
Patent number
US09062070B2

Reaction notes

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