Dichloromethane → HCID 59013467, compound

HRID 1716973Notes

Reaction equation

HRID 1716973 reaction equation
[O:1]=[O+][O-].[CH2:4]([CH:7]1[C:53]2[C:48](=[CH:49][C:50]([CH2:55][C:56]3[CH:61]=[CH:60][C:59]([CH2:62][CH3:63])=[CH:58][CH:57]=3)=C(Cl)[CH:52]=2)[C@:9]2([C@H:14]([O:15]CC3C=CC=CC=3)[C@@H:13]([O:23]CC3C=CC=CC=3)[C@H:12]([O:31]CC3C=CC=CC=3)[C@@H:11]([CH2:39][O:40]CC3C=CC=CC=3)[O:10]2)[CH2:8]1)[CH:5]=C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[BH4-].[Na+].[CH2:85]([Cl:87])Cl>>[Cl:87][C:85]1[CH:52]=[C:53]2[C:48](=[CH:49][C:50]=1[CH2:55][C:56]1[CH:57]=[CH:58][C:59]([CH2:62][CH3:63])=[CH:60][CH:61]=1)[C@:9]1([C@H:14]([OH:15])[C@@H:13]([OH:23])[C@H:12]([OH:31])[C@@H:11]([CH2:39][OH:40])[O:10]1)[CH2:8][CH:7]2[CH2:4][CH2:5][OH:1]

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 11776TriphenylphosphineHCID 24823OzoneHCID 4311764Sodium borohydrideHCID 59013477HCID 59013477, compound

Product 1

HCID 59013467HCID 59013467, compound

Procedure

O3 was bubbled into a cooled solution (−78° C.) of (1S,3′R,4′S,5′R,6′R)-3-allyl-3′,4′,5′-tris(benzyloxy)-6′-(benzyloxymethyl)-5-chloro-6-(4-ethylbenzyl)-2,3,3′,4′,5′,6′-hexahydrospiro[indene-1,2′-pyran] (100 mg, 0.12 mmol) in CH2Cl2 (20 mL). After 5 min, N2 was bubbled into this solution for 20 min while the reaction temperature was gradually raised to room temperature. PPh3 (50 mg, 0.24 mmol) was added and the resulting mixture was stirred for 1 h at room temperature and concentrated. The resulting crude aldehyde was dissolved in THF (20 mL), and NaBH4 (9 mg, 0.24 mmol) was added. After being stirred at room temperature for 2 h, the reaction mixture was quenched by saturated aqueous NH4Cl solution and concentrated. The residue was partitioned between water and AcOEt, the organic layer was separated, washed with brine and dried over Na2SO4. Concentration and purification by preparative HPLC gave 85 mg (95%) of tetra-benzyl-protected alcohol, which was deprotected using the standard hydrogenation procedure to provide the title compound (30 mg). 1H NMR (CD3OD, 300 MHz) δ 7.26 (s, 1H), 7.24 (s, 1H), 7.09 (m, 4H), 4.05 (s, 2H), 3.82-3.21 (m, 9H), 2.77 (dd, J=12.9, 7.8 Hz, 1H), 2.58 (q, J=7.8 Hz, 2H), 2.13 (m, 1H), 1.77 (dd, J=12.9, 7.8 Hz, 1H), 1.68 (m, 1H), 1.19 (t, J=7.8 Hz, 3H); MS ESI (m/z) 463 (M+1)+, calc. 460.

Workup

  1. customN2 was bubbled into this solution for 20 min while the reaction temperature
  2. concentrationconcentrated
  3. dissolutionThe resulting crude aldehyde was dissolved in THF (20 mL)
  4. stirringAfter being stirred at room temperature for 2 h
  5. customthe reaction mixture was quenched by saturated aqueous NH4Cl solution
  6. concentrationconcentrated
  7. customThe residue was partitioned between water and AcOEt
  8. customthe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over Na2SO4
  11. concentrationConcentration and purification by preparative HPLC
  12. customgave 85 mg (95%) of tetra-benzyl-protected alcohol, which

Sources & evidence

ORD record
ord-ca79db1b626f449ba9e986fa8daa429d
Source dataset
uspto-grants-2010_09
Patent number
US07803778B2

Reaction notes

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