Propylamine → HCID 67480231, compound

HRID 2273034Notes

Reaction equation

HRID 2273034 reaction equation
[CH2:1]([O:8][C@@H:9]1[C@H:14]2[NH:15][C:16](=O)[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C@H:10]1[OH:28])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O(C)S(C(F)(F)F)(=O)=O.[CH2:38]([NH2:41])[CH2:39][CH3:40]>C(Cl)Cl>[CH2:1]([O:8][C@@H:9]1[C@H:14]2[N:15]=[C:16]([NH:41][CH2:38][CH2:39][CH3:40])[O:17][C@H:13]2[CH2:12][C@H:11]([CH2:19][O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[C@H:10]1[OH:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 7852PropylamineHCID 9526Methyl triflateHCID 67480227HCID 67480227, compound

Product 1

HCID 67480231HCID 67480231, compoundYield 30.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (3aS,4R,5R,6R,7aS)-4-(benzyloxy)-6-((benzyloxy)methyl)-5-hydroxyhexahydrobenzo[d]oxazol-2(3H)-one (60 mg, 0.16 mmol) in dry DCM (2 mL) under N2 at 0° C. was added methyl triflate (0.035 mL, 0.32 mmol) dropwise. The mixture was stirred at room temperature for 18 h, cooled to 0° C. and n-propylamine (0.131 mL, 1.6 mmol) was added. The mixture was further stirred at 0° C. for 5 h. The mixture was diluted with aqueous satd. NaHCO3 (15 mL) and extracted with DCM (2×15 mL). The extracts were dried (Na2SO4) and concentrated to give the crude product (75 mg). This was purified by silica gel chromatography, eluted with 92:6:2 DCM-MeOH—NH4OH to give the product (3aS,4R,5R,6R,7aS)-4-(benzyloxy)-6-((benzyloxy)methyl)-2-(propylamino)-3a,4,5,6,7,7a-hexahydrobenzo[d]oxazol-5-ol (21 mg, 30.6%). 1H NMR (600 MHz, CDCl3) δ 7.35-7.27 (m, 10H), 4.94 (d, J=11.6, 1H), 4.85 (m, 1H), 4.71 (d, J=8.2, 1H), 4.53 (s, 2H), 4.02 (t, J=6.8, 1H), 3.68 (m, 3H), 3.50 (t, J=6.4, 1H), 3.75 (m, 2H), 2.18-2.15 (dt, J=14.8, 3.0, 1H), 1.98-1.94 (m, 1H), 1.80-1.78 (m, 1H), 1.62-1.58 (m, 2H), 0.98 (t, J=7.2, 3H).

Workup

  1. temperaturecooled to 0° C.
  2. stirringThe mixture was further stirred at 0° C. for 5 h
  3. additionThe mixture was diluted with aqueous satd
  4. extractionNaHCO3 (15 mL) and extracted with DCM (2×15 mL)
  5. dry with materialThe extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customto give the crude product (75 mg)
  8. customThis was purified by silica gel chromatography
  9. washeluted with 92:6:2 DCM-MeOH—NH4OH

Sources & evidence

ORD record
ord-df76fb6adb4b46b7965d1a1089616cca
Source dataset
uspto-grants-2015_09
Patent number
US09120781B2

Reaction notes

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