Sodium borohydride → (R)-ethyl 4-((2R,4S,6S)-6-((S)-4-(tert-butyldiphenylsilyloxy)-2-(4-methoxybenzyloxyl)butyl)-4-hydroxytetrahydro-2H-pyran-2-yl)-3-(trimethylsilyloxy)butanoate

HRID 509213Notes

Reaction equation

HRID 509213 reaction equation
[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=1)[CH2:22][C@H:23]1[O:28][C@@H:27]([CH2:29][C@@H:30]([O:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26][C:25](=[O:42])[CH2:24]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[Si:1]([O:18][CH2:19][CH2:20][C@H:21]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([O:51][CH3:52])=[CH:47][CH:46]=1)[CH2:22][C@H:23]1[O:28][C@@H:27]([CH2:29][C@@H:30]([O:37][Si:38]([CH3:40])([CH3:39])[CH3:41])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:26][C@@H:25]([OH:42])[CH2:24]1)([C:14]([CH3:16])([CH3:15])[CH3:17])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 131733242(R)-ethyl 4-((2S,6R)-6((S)-4-(tert-butyldiphenylsilyloxy)-2-(4-methoxybenzyloxyl)butyl)-4-oxotetrahydro-2H-pyran-2-yl)-3-(trimethylsilyloxy)butanoate

Product 1

HCID 131733241(R)-ethyl 4-((2R,4S,6S)-6-((S)-4-(tert-butyldiphenylsilyloxy)-2-(4-methoxybenzyloxyl)butyl)-4-hydroxytetrahydro-2H-pyran-2-yl)-3-(trimethylsilyloxy)butanoateYield 94%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of ketone 17 (59.0 mg, 0.0788 mmol, 1.0 equiv) in MeOH (5.0 mL, 0.015M) in a 15 mL rb flask at 0° C. was added NaBH4 (6.0 mg, 0.158 mmol, 2.0 equiv) in one portion. After 30 min at 0° C., the reaction was quenched by addition of acetone (0.1 mL), and then concentrated under reduced pressure. Purification was accomplished by flash chromatography column on a 3×12 cm column, eluting with 40% EtOAc/hexanes, collecting 18×150 mm test tube fractions. The product containing fractions (6-10) were combined and concentrated under reduced pressure to give the alcohol product 4 (55.6 mg, 94% yield) as colorless oil: Rf=0.40 (50% EtOAc/Hexanes); [α]D20=+16 (c=0.29, CHCl3); 500 MHz 1H NMR (CDCl3) δ 7.70-7.66 (m, 4H), 7.46-7.37 (m, 6H), 7.17 (d, J=8.7 Hz, 2H), 6.84 (d, J=8.7 Hz, 2H), 4.45 (d, J=10.8 Hz, 1H), 4.38 (d, J=11.1 Hz, 1H), 4.40-4.32 (m, 1H), 4.15-4.02 (dddddd, J=18.1, 10.7, 10.7, 7.1, 7.1, 7.1 Hz, 2H), 3.91-3.86 (m, 1H), 3.82-3.74 (m, 7H), 3.56-3.50 (m, 1H), 3.46-3.39 (m, 1H), 2.50 (d, J=5.5 Hz, 1H), 2.49 (d, J=3.0 Hz, 1H), 1.97 (ddd, J=12.4, 4.4, 2.4 Hz, 1H), 1.90-1.76 (m, 4H), 1.68-1.45 (m, 5H), 1.20 (t, J=7.1 Hz, 3H), 1.06 (s, 9H), 0.12 (s, 9H); 125 MHz 13C NMR (CDCl3) δ 171.8, 159.3, 135.8, 135.8, 134.1, 134.1, 131.2, 129.8, 129.5, 127.9, 127.9, 114.0, 72.9, 72.1, 72.1, 71.7, 68.3, 66.8, 60.7, 60.5, 55.5, 43.9, 42.9, 42.3, 41.8, 41.5, 37.8, 27.1, 19.4, 14.4, 0.5; 125 MHz DEPT 13C NMR (CDCl3) CH3 δ 55.5, 27.1, 14.4, 0.5; CH2 δ 71.7, 60.7, 60.5, 43.9, 42.9, 42.3, 41.8, 41.5, 37.8; CH δ 135.8, 135.8, 129.8, 129.5, 127.9, 127.9, 114.0, 72.9, 72.1, 68.4, 66.8; C δ 171.8, 159.3, 134.1, 134.1, 131.2, 19.4; IR (neat) 3440, 2940, 1735, 1612, 1513, 1428, 1376, 1250, 1175, 1109, 1037, 741, 704, 613, 536 cm−1; HRMS (ESI/APCI) calcd for C42H62O8Na (M+Na) 773.3881. found 773.3886.

Workup

  1. customthe reaction was quenched by addition of acetone (0.1 mL)
  2. concentrationconcentrated under reduced pressure
  3. customPurification
  4. washeluting with 40% EtOAc/hexanes
  5. customcollecting 18×150 mm test tube fractions
  6. additionThe product containing fractions (6-10)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-92501e31bd3344f99c91c294afacb7d7
Source dataset
uspto-grants-2015_08
Patent number
US09096550B2

Reaction notes

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