Phosphoric Acid → [1-Amino-3-[(6R)-6-hexyl-5,6,7,8-tetrahydro-2-naphthalenyl]cyclopentyl]methyl dihydrogen phosphate

HRID 516956Notes

Reaction equation

HRID 516956 reaction equation
[O:1]=[P:2]12[O:13]P3(OP(OP(O3)([O:9]1)=O)(=O)[O:3]2)=O.P(=O)(O)(O)O.[NH2:20][C@:21]1([CH2:42]O)[CH2:25][CH2:24][C@H:23]([C:26]2[CH:35]=[CH:34][C:33]3[CH2:32][C@H:31]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:30][CH2:29][C:28]=3[CH:27]=2)[CH2:22]1>O>[P:2]([OH:13])([OH:9])([O:3][CH2:42][C@@:21]1([NH2:20])[CH2:25][CH2:24][C@H:23]([C:26]2[CH:35]=[CH:34][C:33]3[CH2:32][C@H:31]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[CH2:30][CH2:29][C:28]=3[CH:27]=2)[CH2:22]1)=[O:1]

Participants

5

Reactant 3

HCID 1004Phosphoric AcidHCID 14812Phosphorus oxide (P4O10)HCID 77050638((1R,3S)-1-AMINO-3-((R)-6-HEXYL-5,6,7,8-TETRAHYDRONAPHTHALEN-2-YL)CYCLOPENTYL)METHANOL

Product 1

HCID 78321974[1-Amino-3-[(6R)-6-hexyl-5,6,7,8-tetrahydro-2-naphthalenyl]cyclopentyl]methyl dihydrogen phosphateYield 52.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of phosphorus pentoxide (150 mg, 0.528 mmol) and 85% phosphoric acid (0.15 mL, 10.01 μmol) was stirred at 100° C. under nitrogen for 1 h before ((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (Example 1, 6 mg, 0.018 mmol) was added. The solution was stirred at the same temperature for 3 h. Water (0.5 mL) was added at room temperature. The mixture was stirred at room temperature for 1 h. Purification using reverse phase HPLC (PHENOMENEX® Luna Axia 5μ c18 30×100 mm, 10 minute run, Solvent A: 10% MeOH: 90% H2O: 0.1% TFA, Solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, and lyophilization gave ((1R,3S)-1-amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methyl dihydrogen phosphate (4 mg, 9.38 μmol) as a white solid. LC/MS M+1=410. HPLC retention time=3.96 min (Condition C). 1H NMR (400 MHz, methanol-d4+CDCl3) δ 7.10-6.83 (m, 3H), 4.06-3.77 (m, 2H), 3.20-3.06 (m, 1H), 2.85-2.74 (m, 2H), 2.48 (dd, J=12.9, 6.9 Hz, 1H), 2.40-2.28 (m, 1H), 2.19-2.08 (m, 1H), 2.05-1.90 (m, 4H), 1.80-1.62 (m, 2H), 1.48-1.22 (m, 12H), 0.95-0.86 (m, 3H).

Workup

  1. additionwas added
  2. stirringThe mixture was stirred at room temperature for 1 h
  3. customPurification
  4. concentrationphase HPLC (PHENOMENEX® Luna Axia 5μ c18 30×100 mm, 10 minute run, Solvent A: 10% MeOH: 90% H2O: 0.1% TFA, Solvent B: 90% MeOH, 10% H2O, 0.1% TFA), concentration, and lyophilization

Sources & evidence

ORD record
ord-c97398e550cc4c1fb412d22ee7918c9b
Source dataset
uspto-grants-2015_08
Patent number
US09115054B2

Reaction notes

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