Carbon Tetrachloride → 17-cyclopropylmethyl-7alpha-[(2S)-3,3-dimethyl-2-hydroxybutan-2-yl]-4,5alpha-epoxy-3,6-dihydroxy-6alpha,14alpha-ethanomorphinan

HRID 629828Notes

Reaction equation

HRID 629828 reaction equation
[CH3:1][C@@:2]([OH:34])([C:30]([CH3:33])([CH3:32])[CH3:31])[C@@H:3]1[C@:8]2([O:28]C)[C@@H:9]3[O:23][C:18]4=[C:19]([OH:22])[CH:20]=[CH:21][C:16]5=[C:17]4[C@:10]43[CH2:11][CH2:12][N:13]([CH2:24][CH:25]3[CH2:27][CH2:26]3)[C@H:14]([CH2:15]5)[C@@:5]4(CC2)[CH2:4]1.C(Cl)(Cl)(Cl)Cl.[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:46]1COC[CH2:47]1>>[CH:25]1([CH2:24][N:13]2[CH2:12][CH2:11][C@@:10]34[C:17]5[C:16]6[CH2:15][C@@H:14]2[C@H:5]3[CH2:4][C@H:3]([C@:2]([OH:34])([C:30]([CH3:32])([CH3:33])[CH3:31])[CH3:1])[C@H:8]([OH:28])[C@@H:9]4[O:23][C:18]=5[C:19]([OH:22])=[C:20]2[CH2:47][CH2:46][C:21]2=6)[CH2:27][CH2:26]1

Participants

5

Reactant 4

HCID 5943Carbon TetrachlorideHCID 8028Tetrahydrofuran2×HCID 9848990Buprenorphine component OF alks-5461HCID 21226445Aluminium lithium hydride

Product 1

HCID 8671165917-cyclopropylmethyl-7alpha-[(2S)-3,3-dimethyl-2-hydroxybutan-2-yl]-4,5alpha-epoxy-3,6-dihydroxy-6alpha,14alpha-ethanomorphinan

Conditions

Temperature
55 °C

Procedure

To a solution of buprenorphine (1) (10.0 g, 21.58 mMol) in CCl4 (21.7 ml, 224.5 mMol) and THF (200 ml) was added at 0° C. LiAlH4 (320 ml, 1.0 M, 320 mMol) in THF. The reaction mixture was heated to 55° C. for 24 h. The resulting reaction mixture was cooled to 0° C. and the reaction was quenched by slow, portion-wise addition of Na2SO4·10H2O (103 g), followed by addition of EtOAc (400 ml). After 20 minutes agitation, the resulting slurry was filtered through the pre-packed Solka Floc-40 (18 g). The resulting wet cake was washed thoroughly with EtOAc (2×100 ml). The combined filtrate was concentrated to dryness, affording 13.5 g of crude compound 2 which was subsequently purified by column chromatography on silica gel to afford 6.03 g of compound 2 (62.2% yield) as a white solid with a purity of >99%.

Workup

  1. customThe resulting reaction mixture
  2. temperaturewas cooled to 0° C.
  3. customthe reaction was quenched by slow,
  4. additionportion-wise addition of Na2SO4·10H2O (103 g)
  5. additionfollowed by addition of EtOAc (400 ml)
  6. filtrationthe resulting slurry was filtered through the pre-packed Solka Floc-40 (18 g)
  7. washThe resulting wet cake was washed thoroughly with EtOAc (2×100 ml)
  8. concentrationThe combined filtrate was concentrated to dryness

Sources & evidence

ORD record
ord-4259389cfeb24af78dc9eaa037469ebf
Source dataset
uspto-grants-2016_04
Patent number
US09315514B2

Reaction notes

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