Triethylamine → HCID 23648353, compound

HRID 132151Notes

Reaction equation

HRID 132151 reaction equation
[CH:1]1([CH2:7][CH2:8][C@H:9]([NH:29][C:30](=[O:39])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=2)[C:10]([NH:12][C@H:13]([CH2:18][N:19]2[C:27]3[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=3)[CH2:21][CH2:20]2)[CH2:14][C:15](O)=[O:16])=[O:11])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[CH:1]1([CH2:7][CH2:8][C@H:9]([NH:29][C:30](=[O:39])[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([O:37][CH3:38])[CH:32]=2)[C:10](=[O:11])[NH:12][C@H:13]([CH2:18][N:19]2[C:27]3[C:22](=[CH:23][C:24]([F:28])=[CH:25][CH:26]=3)[CH2:21][CH2:20]2)[CH2:14][CH2:15][OH:16])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 11249688HCID 11249688, compound

Product 1

HCID 23648353HCID 23648353, compoundYield 51.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A sample of the title compound of example 47 (114 mg, 0.21 mmol) in THF (5 mL) was cooled in an ice/water bath and treated with triethylamine (21 mg, 0.21 mmol) followed by isobutyl chloroformate. After stirring for 25 minutes, the solution was transferred to a precooled (ice/water bath) stirring solution of excess NaBH4 in water (5 mL). After stirring for 1 hour, the solution was quenched by addition of excess 1 M HCl at 0° C. The reaction was diluted with ethyl acetate and extracted with 1 M NaOH solution. The organics were dried over MgSO4 and the solvent was removed. The residue was purified on silica gel using a gradient of 0 to 100% ethyl acetate in hexane to afford 57 mg (51%) of the title material as a solid; 1H NMR (CDCl3, 400 MHz) δ 0.65-0.82 (m, 2H), 1.00-1.25 (m, 6H), 1.47-1.66 (m, 6H), 1.66-1.78 (m, 2H), 1.82-1.97 (m, 2H), 2.88-2.95 (m, 2H), 3.01 (dd, 1H, J1=5.6, J2=13.7), 3.21 (dd, 1H, J1=7.7, J2=13.7), 3.29 (dd, 1H, J1=8.7, J2=17.3), 3.44-3.52 (m, 1H), 3.55-3.68 (m, 2H), 3.83 (s, 3H), 4.31-4.41 (m, 1H), 4.64 (dd, 1H, J1=6.9, J2=14.1), 6.34 (dd, 1H, J1=4.1, J2=8.6), 6.568 (ddd, 1H, J1=2.5, J2=J3=8.9), 6.79 (dd, 1H, J1=2.4, J2=8.3), 7.03-7.08 (m, 1H), 7.15 (d, 1H, J=7.7), 7.22 (d, 1H, J=8.8), 7.29-7.35 (m, 3H); HPLC-MS calcd. for C30H40FN3O4 (M+H+) 526.3, found 526.5.

Workup

  1. stirringAfter stirring for 1 hour
  2. customthe solution was quenched by addition of excess 1 M HCl at 0° C
  3. additionThe reaction was diluted with ethyl acetate
  4. extractionextracted with 1 M NaOH solution
  5. dry with materialThe organics were dried over MgSO4
  6. customthe solvent was removed
  7. customThe residue was purified on silica gel using a gradient of 0 to 100% ethyl acetate in hexane

Sources & evidence

ORD record
ord-c1ede389f81b45e387092d9246197564
Source dataset
uspto-grants-2008_06
Patent number
US07384970B2

Reaction notes

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