4-Methoxybenzyl alcohol → 4-Methoxybenzyl {(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pent-4-yn-1-yl}carbamate

HRID 713707Notes

Reaction equation

HRID 713707 reaction equation
[Si:1]([O:8][C@H:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@@H:10]([CH2:14][CH2:15][C:16]#[CH:17])C(O)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([N:26]([CH2:29]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:38])C=CC=CC=1.[CH3:48][O:49][C:50]1[CH:57]=[CH:56][C:53]([CH2:54][OH:55])=[CH:52][CH:51]=1>C1(C)C=CC=CC=1.C(=O)(O)[O-]>[Si:1]([O:8][C@H:9]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C@H:10]([NH:26][C:29](=[O:38])[O:55][CH2:54][C:53]1[CH:56]=[CH:57][C:50]([O:49][CH3:48])=[CH:51][CH:52]=1)[CH2:14][CH2:15][C:16]#[CH:17])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 77384-Methoxybenzyl alcoholHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 57907531(2R)-2-[(S)-{[Tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]hex-5-ynoic acid

Product 1

HCID 579075124-Methoxybenzyl {(1R)-1-[(R)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]pent-4-yn-1-yl}carbamateYield 90.7%

Reagents, catalysts & solvents 2

HCID 769Bicarbonate IonSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 40.0 g (120 mmol) of (2R)-2-[(8)-{[tert-butyl(dimethyl)silyl]oxy}(phenyl)methyl]hex-5-ynoic acid from Step D above and 33.5 mL (241 mmol) of triethylamine in 400 mL of anhydrous toluene at ambient temperature under an atmosphere of nitrogen was added 37.5 mL (132 mmol) of diphenylphosphoryl azide. The mixture was stirred for 5 h and then 37.5 mL (301 mmol) of 4-methoxybenzyl alcohol was added. The resulting mixture was heated to 105° C. for 16 h, cooled to ambient temperature and then diluted with 250 mL of a saturated aqueous bicarbonate solution. The phases were separated and the aqueous phase was extracted with ethyl acetate (2×150 mL). The combined organics were washed with water (100 mL), brine (100 mL) then dried over magnesium sulfate, filtered and evaporated in vacuo. The crude residue was purified by silica gel chromatography eluting with 3-10% ethyl acetate in hexanes to afford the title compound as a colorless oil (50.9 g, 90.5%). 1H NMR (500 MHz, CDCl3): 7.28-7.21 (m, 7H), 6.87 (d, J=8.4 Hz, 2H), 4.92 (s, 2H), 4.77-4.59 (m, 2H), 3.89-3.84 (m, 1H), 3.81 (s, 3H), 2.30-2.22 (m, 2H), 1.95 (m, 1H), 1.91-1.85 (m, 1H), 1.57-1.50 (m, 1H), 0.89 (s, 9H), 0.06 (s, 3H), −0.15 (s, 3H). LC-MS: m/z (ES) 468.1 (MH)+, 490.0 (MNa)+.

Workup

  1. temperaturecooled to ambient temperature
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with ethyl acetate (2×150 mL)
  4. washThe combined organics were washed with water (100 mL), brine (100 mL)
  5. dry with materialthen dried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude residue was purified by silica gel chromatography
  9. washeluting with 3-10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-05c6b6716c204b008443954b9c08f375
Source dataset
uspto-grants-2015_11
Patent number
US09186354B2

Reaction notes

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