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

HRID 1399526Notes

Reaction equation

HRID 1399526 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8](=[O:12])[C@H:9](O)[CH3:10])[CH:5]=[CH:6][CH:7]=1.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.[NH2:44][C:45]([CH3:49])([CH3:48])[CH2:46][OH:47]>C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([C@:8]2([OH:12])[O:47][CH2:46][C:45]([CH3:49])([CH3:48])[NH:44][C@H:9]2[CH3:10])[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 118072-Amino-2-methyl-1-propanolHCID 67749Trifluoromethanesulfonic anhydrideHCID 88675Proton spongeHCID 46838073(R)-1-(3-bromophenyl)-2-hydroxypropan-1-one

Product 1

HCID 46837649(2S,3S)-2-(3-bromophenyl)-3,5,5-trimethylmorpholin-2-olYield 39%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Compound 4d was synthesized by a procedure similar to that described for (2S,3S)-4a using (R)-1-(3-bromophenyl)-2-hydroxypropan-1-one (10d, 4.0 g, 0.018 mol), Proton sponge (4.5 g, 0.021 mol), triflic anhydride (3.2 mL, 192 mmol), and 2-amino-2-methyl-1-propanol (3.4 g, 0.038 mol) in acetonitrile (50 mL). After purification, 2.04 g (39%) of the free base 4d was isolated and converted to 1.6 g of the hemi-D-tartrate salt, which had >99% ee: mp 129-130° C.; [α]20D +9.6° (c 1.0, CH3OH); 1H NMR (methanol-d4) δ 7.77-7.76 (m, 1H), 7.63-7.53 (m, 2H), 7.38-7.32 (m, 1H), 4.37 (s, 1H), 4.14 (d, 1H, J=12.0 Hz), 3.58-3.39 (m, 2H), 1.57 (s, 3H), 1.32 (s, 3H), 1.07-1.02 (m, 3H); 13C NMR (methanol-d4) δ 178.8, 145.1, 133.3, 131.1, 126.9, 123.6, 96.7, 75.2, 67.7, 55.0, 24.4, 21.5, 14.4; LCMS (ESI) m/z 300.6 [(M-tartrate)+, M=C15H21BrNO5]; Anal. (C15H21BrNO5.0.25H2O) calcd: C, 47.44; H 5.71; N, 3.69. found: C, 47.33; H, 5.84; N, 3.63.

Workup

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

Sources & evidence

ORD record
ord-8dacdaf9d2ea4f76980340b94dc62e25
Source dataset
uspto-grants-2014_12
Patent number
US08906908B2

Reaction notes

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