Triethylamine → HCID 9858056, compound

HRID 2308021Notes

Reaction equation

HRID 2308021 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([CH2:20][C:21](=[O:31])[NH:22][C@H:23]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH3:24])[CH2:16][C:17](O)=[O:18])=[CH:11][CH:10]=1.ClC(OCC(C)C)=O>O1CCCC1>[C:25]1([C@@H:23]([NH:22][C:21](=[O:31])[CH2:20][C@H:15]([C:12]2[CH:11]=[CH:10][C:9]([F:8])=[CH:14][CH:13]=2)[CH2:16][CH2:17][OH:18])[CH3:24])[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 9967248HCID 9967248, compound

Product 1

HCID 9858056HCID 9858056, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3 mL of triethylamine was added to a solution of 5 g of compound 7a in 200 mL of tetrahydrofuran at room temperature. The solution was stirred for 60 min at room temperature and then was moved to a −78° C. dry ice acetone bath. To this solution was added dropwise 2.6 mL of iso-butyl chloroformate. The suspension was stirred from −78° C. to room temperature overnight. The mixture was filtered through a celite and silica gel pad, and washed with small amount tetrahydrofuran. To this solution in an ice bath was added 2.0 g of sodium borohydride, followed by dropwise addition of 10 mL of water. Carbon dioxide gas evolved violently. The reaction mixture was stirred for 2-4 hr, and was filtered through a celite pad. After the solvent evaporated, the aqueous layer was extracted several times with ethyl acetate. The organic layer was combined, washed with brine, dried over magnesium sulfate, and concentrated. The solid was recrystallized from ethyl acetate and hexanes to form the title compound as a colorless solid (80% yield, 95% de): mp 170.0-170.5° C.; [α]25D=−86.4 (c 1.0, CH3OH); 1H NMR (200 MHz, CDCl3) δ 7.40-7.10 (m, 7 H), 6.98 (t, J=8.7Hz, 2 H), 5.51 (br d, J=7.7 Hz, 1 H), 5.00 (quint, J=7.4 Hz, 1 H), 3.60-3.50 (m, 2 H), 3.33 (m, 1 H), 2.55 (dd, J=6.6, 14.2 Hz, 1 H), 2.38 (dd, J=8.6, 14.2 Hz, 1 H), 1.95-1.75 (m, 2 H), 1.27 (d, J=6.9 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 170.6, 161.6, 142.9, 139.6, 128.9, 128.6, 127.4, 126.1, 115.4, 60.1, 48.6, 44.0, 38.9, 38.4, 21.3. Anal. Calcd for C19H22FNO2: C, 72.36; H, 7.03; N, 4.44. Found: C, 72.35; H, 6.83; N, 4.33.

Workup

  1. customwas moved to a −78° C.
  2. stirringThe suspension was stirred from −78° C. to room temperature overnight
  3. filtrationThe mixture was filtered through a celite and silica gel pad
  4. washwashed with small amount tetrahydrofuran
  5. additionTo this solution in an ice bath was added 2.0 g of sodium borohydride
  6. additionfollowed by dropwise addition of 10 mL of water
  7. stirringThe reaction mixture was stirred for 2-4 hr
  8. filtrationwas filtered through a celite pad
  9. customAfter the solvent evaporated
  10. extractionthe aqueous layer was extracted several times with ethyl acetate
  11. washwashed with brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated
  14. customThe solid was recrystallized from ethyl acetate and hexanes

Sources & evidence

ORD record
ord-4555e324e7de4f1db23e8146a4d1e980
Source dataset
uspto-grants-2004_12
Patent number
US06833458B2

Reaction notes

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