Water → (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine

HRID 2360324Notes

Reaction equation

HRID 2360324 reaction equation
[Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@H:7]2[CH2:11][O:10][CH2:9][C@H:8]2[NH2:12])=[CH:4][CH:3]=1.[C@:15]12([CH2:25][S:26]([OH:29])(=[O:28])=[O:27])[C:22]([CH3:24])([CH3:23])[CH:19]([CH2:20][CH2:21]1)[CH2:18][C:16]2=[O:17].O>CC(O)C>[C:15]12([CH2:25][S:26]([OH:29])(=[O:27])=[O:28])[C:22]([CH3:24])([CH3:23])[CH:19]([CH2:20][CH2:21]1)[CH2:18][C:16]2=[O:17].[Br:1][C:2]1[CH:14]=[CH:13][C:5]([O:6][C@@H:7]2[CH2:11][O:10][CH2:9][C@@H:8]2[NH2:12])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 962WaterHCID 218580(1S)-(+)-Camphor-10-sulphonic acidHCID 67193588cis-4-(4-Bromophenoxy)tetrahydrofuran-3-amine

Product 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 67193589(3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amineYield 43%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A mixture of cis-4-(4-bromophenoxy)tetrahydrofuran-3-amine (191 g, 0.74 mol) and (1S)-(+)-10-camphorsulfonic acid (154.2 g, 0.66 mol) was dissolved in 2-propanol (2.4 L) and water (100 mL) at reflux. The clear solution was allowed to cool to room temperature over 18 hours, and the resulting crystals were isolated, washed and dried to afford the (+)-camphorsulfonic acid salt of (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine (139.2 g, 0.284 mol) with an e.e. (enantiomeric excess) of 85%. Recrystallization from 2-propanol (1.2 L) and water (70 mL) afforded the (+)-camphorsulfonic acid salt of (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine, with an e.e. of 99%. Yield: 113.2 g, 0.23 mol, 31%. 1H NMR (300 MHz, DMSO-d6) δ 0.74 (s, 3H), 1.05 (s, 3H), 1.23 (d, half of AB quartet J=10 Hz, 1H), 1.29 (d, half of AB quartet, J=10 Hz, 1H), 1.76-1.94 (m, 2H), 2.19-2.28 (m, estimated 2H), 2.35 (d, J=14.7 Hz, 1H), 2.66-2.73 (m, estimated 1H), 2.85 (d, J=14.7 Hz, 1H), 3.78-3.84 (m, 2H), 3.96-4.10 (m, 3H), 5.04 (m, 1H), 6.99 (d, J=8.8 Hz, 2H), 7.52 (d, J=9.0 Hz, 2H), 8.23 (br s, 3H). Additional (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine(+)-camphorsulfonic acid salt (13.6 g, 27.7 mmol) from another experiment was added and the combined batch (126.8 g, 0.258 mol) was washed with 2N aqueous sodium hydroxide solution and extracted three times with methylene chloride. The organic layers were combined and concentrated in vacuo, affording (3S,4S)-4-(4-bromophenoxy)tetrahydrofuran-3-amine as a white solid with an e.e. of 99%. Yield: 65.6 g, 0.254 mmol, 98% for neutralization.

Workup

  1. customthe resulting crystals were isolated
  2. washwashed
  3. customdried

Sources & evidence

ORD record
ord-8ad0fc55a6a9449a9c57de5862449fdc
Source dataset
uspto-grants-2014_04
Patent number
US08686043B2

Reaction notes

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