HCID 67274604, compound → [2-methoxy-5-[(3R,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)-2-hydroxytetrahydropyran-2-yl]phenyl]-spiro[chromane-2,1'-cyclobutane]-6-yl-methanone

HRID 1258830Notes

Reaction equation

HRID 1258830 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[O:11][C:7]1([CH2:10][CH2:9][CH2:8]1)[CH2:6][CH2:5]2.C([Li])CCC.[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:27]([C:30]2([OH:69])[C@H:35]([O:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C@@H:34]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C@H:33]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C@@H:32]([CH2:60][O:61][CH2:62][C:63]3[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=3)[O:31]2)=[CH:26][C:23]=1[CH:24]=[O:25]>C1COCC1.C1(C)C=CC=CC=1>[CH3:20][O:21][C:22]1[CH:29]=[CH:28][C:27]([C:30]2([OH:69])[C@H:35]([O:36][CH2:37][C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C@@H:34]([O:44][CH2:45][C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[C@H:33]([O:52][CH2:53][C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[C@@H:32]([CH2:60][O:61][CH2:62][C:63]3[CH:64]=[CH:65][CH:66]=[CH:67][CH:68]=3)[O:31]2)=[CH:26][C:23]=1[C:24]([C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[O:11][C:7]1([CH2:10][CH2:9][CH2:8]1)[CH2:6][CH2:5]2)=[O:25]

Participants

6

Reactant 3

HCID 67274604HCID 67274604, compoundHCID 866551982-Methoxy-5-((3R,4S,5R,6R)-3,4,5-tris-benzyloxy-6-benzyloxymethyl-2-hydroxy-tetrahydro-pyran-2-yl)-benzaldehydeHCID 178418339Butyllithium

Product 1

HCID 67117063[2-methoxy-5-[(3R,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)-2-hydroxytetrahydropyran-2-yl]phenyl]-spiro[chromane-2,1'-cyclobutane]-6-yl-methanoneYield 65.6%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 6-bromospiro[chromane-2,1′-cyclobutane] (0.563 g, 2.23 mmol) in THF (3 mL) at −78° C. was added n-butyl lithium (1.45 mL, 2.23 mmol) and stirred for 1 h. Compound obtained in step III (0.3 g, 0.45 mmol) in toluene (3 mL) was cooled to −78° C. and Ithium salt prepared above was added to this at −78° C. This reaction mixture was stirred for 1 h, quenched with sat. NH4Cl (10 mL) and extracted with ethyl acetate (2×20 mL). The ethyl acetate layer was washed with water, brine, dried over sodium sulphate, concentrated and purified by silica gel column chromatography to furnish [2-methoxy-5-[(3R,4S,5R,6R)-3,4,5-tribenzyloxy-6-(benzyloxymethyl)-2-hydroxytetrahydropyran-2-yl]phenyl]-spiro[chromane-2,1′-cyclobutane]-6-yl-methanone (0.250 g).

Workup

  1. customIthium salt prepared
  2. additionabove was added to this at −78° C
  3. stirringThis reaction mixture was stirred for 1 h
  4. customquenched with sat. NH4Cl (10 mL)
  5. extractionextracted with ethyl acetate (2×20 mL)
  6. washThe ethyl acetate layer was washed with water, brine
  7. dry with materialdried over sodium sulphate
  8. concentrationconcentrated
  9. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-22f89a6a54914a9d9b11e975cfbfb981
Source dataset
uspto-grants-2013_06
Patent number
US08466114B2

Reaction notes

Loading…