Methyl 5-(3-((1R,2R,3R,5R)-2-((R,E)-7-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate → Methyl 5-(3-((1R,2R,3R,5R)-2-((3S,7R,E)-7-(tert-butyldimethylsilyloxy)-3-hydroxyoct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

HRID 1037723Notes

Reaction equation

HRID 1037723 reaction equation
[Si:1]([O:8][C@H:9]([CH3:42])[CH2:10][CH2:11][CH2:12][C:13](=[O:41])/[CH:14]=[CH:15]/[C@H:16]1[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19][C@@H:18]([Cl:28])[C@@H:17]1[CH2:29][CH2:30][CH2:31][C:32]1[S:36][C:35]([C:37]([O:39][CH3:40])=[O:38])=[CH:34][CH:33]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@H]2N1CCC2.B>ClCCl>[Si:1]([O:8][C@H:9]([CH3:42])[CH2:10][CH2:11][CH2:12][C@H:13]([OH:41])/[CH:14]=[CH:15]/[C@H:16]1[C@H:20]([O:21][CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][O:23]2)[CH2:19][C@@H:18]([Cl:28])[C@@H:17]1[CH2:29][CH2:30][CH2:31][C:32]1[S:36][C:35]([C:37]([O:39][CH3:40])=[O:38])=[CH:34][CH:33]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 57734100Methyl 5-(3-((1R,2R,3R,5R)-2-((R,E)-7-(tert-butyldimethylsilyloxy)-3-oxooct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylateHCID 178419160HCID 178419160, compound

Product 1

HCID 57734084Methyl 5-(3-((1R,2R,3R,5R)-2-((3S,7R,E)-7-(tert-butyldimethylsilyloxy)-3-hydroxyoct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylateYield 81.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of enone 8 (400 mg, 0.62 mmol) in 7 mL of dichloromethane was cooled to −20° C. and stirred rapidly while solid (R)-methylCBS-borane complex 2 (290 mg, 1.0 mmol), was added in one portion. The resulting solution was stirred at −20° to −10° C. for 1 h. TLC analysis at this stage showed no starting material left and the reaction mixture was quenched with 1 mL of methanol, the cooling bath was removed and the mixture was stirred at 20° C. 30 min. The mixture was concentrated in vacuo to remove solvents and the residual products were purified by FCC on silica gel (40 g Silicycle cartridge) to yield 40 mg of (15R+S) isomers and 325 mg of (15S)-alcohol 9; 1H NMR (CDCl3): 0.03 (s, 6H), 0.87 (s, 9H), 1.09 (d, J=6.3 Hz, 3H), 1.30-1.90 (m, 18H), 2.05-2.35 (m, 3H), 2.82 (m, 2H), 3.45 (m, 1H), 3.76 (m, 2H), 3.84 (s, 3H), 3.97 (m, 1H), 4.07 (m, 2H), 4.60 (dt, J=4.2 Hz, 11.1 Hz, 1H), 5.57 (m, 2H), 6.77 (d, J=3.9 Hz, 1H), 7.61 (d, J=3.9 Hz, 1H).

Workup

  1. additionwas added in one portion
  2. waitleft
  3. customthe reaction mixture was quenched with 1 mL of methanol
  4. customthe cooling bath was removed
  5. stirringthe mixture was stirred at 20° C
  6. custom30 min
  7. concentrationThe mixture was concentrated in vacuo
  8. customto remove solvents
  9. customthe residual products were purified by FCC on silica gel (40 g Silicycle cartridge)

Sources & evidence

ORD record
ord-6f3ff266093c4e61ac1accaada0c79c4
Source dataset
uspto-grants-2013_10
Patent number
US08546603B2

Reaction notes

Loading…