Potassium Sodium Tartrate → (S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropan-1-ol

HRID 926200Notes

Reaction equation

HRID 926200 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@H:13]([O:35][C:36]([CH3:43])([CH3:42])[C:37](OCC)=[O:38])[CH2:14][O:15][C:16]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CC(C[AlH]CC(C)C)C.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+].[OH-].[K+]>C(OCC)C.O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH3:12])[C:3]=1[C@H:13]([O:35][C:36]([CH3:43])([CH3:42])[CH2:37][OH:38])[CH2:14][O:15][C:16]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 4

HCID 9357Potassium Sodium TartrateHCID 14487Diisobutylaluminum hydrideHCID 14797Potassium HydroxideHCID 89681793(S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate

Product 1

HCID 89677388(S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropan-1-ol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A solution of (S)-ethyl 2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropanoate (1.58 g, 2.66 mmol) in diethyl ether (62 mL) was treated with DIBAL-H (1.0 M in hexanes, 13.3 mL, 13.3 mmol) at 23° C. After 5 min, aq. Rochelle's salt (excess) was added dropwise over 5 min until bubbling ceased. The quenched reaction was agitated manually for 1 min to ensure full quenching. The system transitioned from a slurry to a gel. 50% w/v aw KOH (10 mL) was added, followed by H2O (40 mL), and the reaction was manually agitated until magnetic stirring was achievable (the reaction transitioned from a gel to a biphasic solution). After 15 min of stirring the reaction was extracted with diethyl ether (3×30 mL). Combined organic layers were dried quickly over MgSO4 for 1 min and promptly filtered and concentrated. The residue was treated with benzene and purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give (S)-2-(1-(1-chloro-3-methylnaphthalen-2-yl)-2-(trityloxy)ethoxy)-2-methylpropan-1-ol. 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J=8.2 Hz, 1H), 7.67 (d, J=7.8 Hz, 1H), 7.52-7.38 (m, 9H), 7.31-7.18 (m, 9H), 5.87 (dd, J=9.5, 3.9 Hz, 1H), 3.76 (d, AB-spin system, J=11.8 Hz, 1H), 3.60 (dd, J=9.6, 9.6 Hz, 1H), 3.32 (d, AB-spin system, J=11.8 Hz, 1H), 3.26 (dd, J=9.8, 3.9 Hz, 1H), 2.49 (s, 3H), 1.16 (s, 3H), 1.02 (s, 3H).

Workup

  1. customuntil bubbling
  2. customThe quenched reaction
  3. additionwas added
  4. stirringthe reaction was manually agitated
  5. stirringuntil magnetic stirring
  6. stirringAfter 15 min of stirring the reaction
  7. extractionwas extracted with diethyl ether (3×30 mL)
  8. dry with materialCombined organic layers were dried quickly over MgSO4 for 1 min
  9. filtrationpromptly filtered
  10. concentrationconcentrated
  11. additionThe residue was treated with benzene
  12. custompurified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e793011fb97f492db1951d5bf19741fc
Source dataset
uspto-grants-2016_03
Patent number
US09284323B2

Reaction notes

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