2-Amino-2-methyl-1-propanol → (2S,3S)-2-(3-Nitrophenyl)-3,5,5-trimethylmorpholin-2-ol

HRID 1399529Notes

Reaction equation

HRID 1399529 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([C:10](=[O:14])[C@H:11](O)[CH3:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].CN(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.[NH2:46][C:47]([CH3:51])([CH3:50])[CH2:48][OH:49]>C(#N)C>[N+:1]([C:4]1[CH:5]=[C:6]([C@:10]2([OH:14])[O:49][CH2:48][C:47]([CH3:51])([CH3:50])[NH:46][C@H:11]2[CH3:12])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 118072-Amino-2-methyl-1-propanolHCID 67749Trifluoromethanesulfonic anhydrideHCID 88675Proton spongeHCID 46838208(R)-1-(3-nitrophenyl)-2-hydroxypropan-1-one

Product 1

HCID 46837652(2S,3S)-2-(3-Nitrophenyl)-3,5,5-trimethylmorpholin-2-olYield 18%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound 4g was synthesized by a procedure similar to that described for (2S,3S)-4a using (R)-1-(3-nitrophenyl)-2-hydroxypropan-1-one (10g, 4.0 g, 0.021 mol), Proton sponge (5.2 g, 0.0246 mol), triflic anhydride (3.7 mL, 0.023 mol), and 2-amino-2-methyl-1-propanol (4.0 g, 0.045 mol) in acetonitrile (45 mL). After purification, 1.0 g (18%) of the free base 4g was isolated and converted to the hemi-D-tartrate salt, which had 94% ee: mp 192-193° C.; [α]20D +6.5° (c 1.0, CH3OH); 1H NMR (methanol-d4) δ 8.47-8.25 (m, 1H), 8.31-8.26 (m, 1H), 8.05-8.01 (m, 1H), 7.73-7.66 (m, 1H), 4.34 (s, 1H), 4.18 (d, 1H, J=12.1 Hz), 3.59 (d, 1H, J=6.6 Hz), 3.50 (q, 1H, J=6.6 Hz), 1.60 (s, 3H), 1.35 (s, 3H), 1.07 (d, 3H, J=6.6 Hz); 13C NMR (methanol-d4) δ 178.3, 149.9, 145.3, 134.4, 131.0, 125.0, 123.0, 96.8, 75.0, 68.1, 54.8, 24.7, 21.7, 14.6; LCMS (ESI) m/z 267.3 [(M-tartrate)', M=C15H21N2O7]; Anal. (C15H21N2O7.0.25H2O) calcd: C, 52.09; H, 6.27; N, 8.10. found: C, 52.13; H, 6.22; N, 8.06.

Workup

  1. customCompound 4g was synthesized by a procedure similar to
  2. customAfter purification

Sources & evidence

ORD record
ord-78a1eb071b01497dbb2784e307a6a271
Source dataset
uspto-grants-2014_12
Patent number
US08906908B2

Reaction notes

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